1932

Abstract

In the last few decades, the AIDS pandemic and the significant advances in the medical management of individuals with neoplastic and inflammatory conditions have resulted in a dramatic increase in the population of immunosuppressed patients with opportunistic, life-threatening fungal infections. The parallel development of clinically relevant mouse models of fungal disease and the discovery and characterization of several inborn errors of immune-related genes that underlie inherited human susceptibility to opportunistic mycoses have significantly expanded our understanding of the innate and adaptive immune mechanisms that protect against ubiquitous fungal exposures. This review synthesizes immunological knowledge derived from basic mouse studies and from human cohorts and provides an overview of mammalian antifungal host defenses that show promise for informing therapeutic and vaccination strategies for vulnerable patients.

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2018-04-26
2024-04-23
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Literature Cited

  1. Brown GD, Denning DW, Gow NA, Levitz SM, Netea MG, White TC. 1.  2012. Hidden killers: human fungal infections. Sci. Transl. Med. 4:165rv13 [Google Scholar]
  2. Fisher MC, Henk DA, Briggs CJ, Brownstein JS, Madoff LC. 2.  et al. 2012. Emerging fungal threats to animal, plant and ecosystem health. Nature 484:186–94 [Google Scholar]
  3. Wu F, Groopman JD, Pestka JJ. 3.  2014. Public health impacts of foodborne mycotoxins. Annu. Rev. Food Sci. Technol. 5:351–72 [Google Scholar]
  4. Kauffman HF. 4.  2006. Innate immune responses to environmental allergens. Clin. Rev. Allergy Immunol. 30:129–40 [Google Scholar]
  5. Iliev ID, Leonardi I. 5.  2017. Fungal dysbiosis: immunity and interactions at mucosal barriers. Nat. Rev. Immunol. 17:635–46 [Google Scholar]
  6. Erwig LP, Gow NA. 6.  2016. Interactions of fungal pathogens with phagocytes. Nat. Rev. Microbiol. 14:163–76 [Google Scholar]
  7. Brown GD. 7.  2011. Innate antifungal immunity: the key role of phagocytes. Annu. Rev. Immunol. 29:1–21 [Google Scholar]
  8. Netea MG, Brown GD, Kullberg BJ, Gow NA. 8.  2008. An integrated model of the recognition of Candida albicans by the innate immune system. Nat. Rev. Microbiol. 6:67–78 [Google Scholar]
  9. Gringhuis SI, Kaptein TM, Wevers BA, Theelen B, van der Vlist M. 9.  et al. 2012. Dectin-1 is an extracellular pathogen sensor for the induction and processing of IL-1β via a noncanonical caspase-8 inflammasome. Nat. Immunol. 13:246–54 [Google Scholar]
  10. Gross O, Poeck H, Bscheider M, Dostert C, Hannesschlager N. 10.  et al. 2009. Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence. Nature 459:433–6 [Google Scholar]
  11. Karki R, Man SM, Malireddi RK, Gurung P, Vogel P. 11.  et al. 2015. Concerted activation of the AIM2 and NLRP3 inflammasomes orchestrates host protection against Aspergillus infection. Cell Host Microbe 17:357–68 [Google Scholar]
  12. Tomalka J, Ganesan S, Azodi E, Patel K, Majmudar P. 12.  et al. 2011. A novel role for the NLRC4 inflammasome in mucosal defenses against the fungal pathogen Candida albicans. . PLOS Pathog 7:e1002379 [Google Scholar]
  13. Ishikawa T, Itoh F, Yoshida S, Saijo S, Matsuzawa T. 13.  et al. 2013. Identification of distinct ligands for the C-type lectin receptors Mincle and Dectin-2 in the pathogenic fungus Malassezia. . Cell Host Microbe 13:477–88 [Google Scholar]
  14. Marakalala MJ, Vautier S, Potrykus J, Walker LA, Shepardson KM. 14.  et al. 2013. Differential adaptation of Candida albicans in vivo modulates immune recognition by Dectin-1. PLOS Pathog 9:e1003315 [Google Scholar]
  15. Sousa MGT, Belda W Jr, Spina R, Lota PR, Valente NS. 15.  et al. 2014. Topical application of imiquimod as a treatment for chromoblastomycosis. Clin. Infect. Dis. 58:1734–37 [Google Scholar]
  16. Sousa MGT, Reid DM, Schweighoffer E, Tybulewicz V, Ruland J. 16.  et al. 2011. Restoration of pattern recognition receptor costimulation to treat chromoblastomycosis, a chronic fungal infection of the skin. Cell Host Microbe 9:436–43 [Google Scholar]
  17. Deng Z, Ma S, Zhou H, Zang A, Fang Y. 17.  et al. 2015. Tyrosine phosphatase SHP-2 mediates C-type lectin receptor–induced activation of the kinase Syk and anti-fungal TH17 responses. Nat. Immunol. 16:642–52 [Google Scholar]
  18. Cao Z, Conway KL, Heath RJ, Rush JS, Leshchiner ES. 18.  et al. 2015. Ubiquitin ligase TRIM62 regulates CARD9-mediated anti-fungal immunity and intestinal inflammation. Immunity 43:715–26 [Google Scholar]
  19. Roth S, Bergmann H, Jaeger M, Yeroslaviz A, Neumann K. 19.  et al. 2016. Vav proteins are key regulators of Card9 signaling for innate antifungal immunity. Cell Rep 17:2572–83 [Google Scholar]
  20. Strasser D, Neumann K, Bergmann H, Marakalala MJ, Guler R. 20.  et al. 2012. Syk kinase-coupled C-type lectin receptors engage protein kinase C-sigma to elicit Card9 adaptor-mediated innate immunity. Immunity 36:32–42 [Google Scholar]
  21. Jia XM, Tang B, Zhu LL, Liu YH, Zhao XQ. 21.  et al. 2014. CARD9 mediates Dectin-1-induced ERK activation by linking Ras-GRF1 to H-Ras for antifungal immunity. J. Exp. Med. 211:2307–21 [Google Scholar]
  22. Gorjestani S, Yu M, Tang B, Zhang D, Wang D, Lin X. 22.  2011. Phospholipase Cγ2 (PLCγ2) is key component in Dectin-2 signaling pathway, mediating anti-fungal innate immune responses. J. Biol. Chem. 286:43651–59 [Google Scholar]
  23. Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M, Wevers B. 23.  et al. 2009. Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-κB activation through Raf-1 and Syk. Nat. Immunol. 10:203–13 [Google Scholar]
  24. Gross O, Gewies A, Finger K, Schafer M, Sparwasser T. 24.  et al. 2006. Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity. Nature 442:651–56 [Google Scholar]
  25. Whitney PG, Bar E, Osorio F, Rogers NC, Schraml BU. 25.  et al. 2014. Syk signaling in dendritic cells orchestrates innate resistance to systemic fungal infection. PLOS Pathog 10:e1004276 [Google Scholar]
  26. Zhao X, Guo Y, Jiang C, Chang Q, Zhang S. 26.  et al. 2017. JNK1 negatively controls antifungal innate immunity by suppressing CD23 expression. Nat. Med. 23:337–46 [Google Scholar]
  27. Xiao Y, Tang J, Guo H, Zhao Y, Tang R. 27.  et al. 2016. Targeting CBLB as a potential therapeutic approach for disseminated candidiasis. Nat. Med. 22:906–14 [Google Scholar]
  28. Romani L, Mencacci A, Cenci E, Del Sero G, Bistoni F, Puccetti P. 28.  1997. An immunoregulatory role for neutrophils in CD4+ T helper subset selection in mice with candidiasis. J. Immunol. 158:2356–62 [Google Scholar]
  29. Lionakis MS, Lim JK, Lee CC, Murphy PM. 29.  2011. Organ-specific innate immune responses in a mouse model of invasive candidiasis. J. Innate Immun. 3:180–99 [Google Scholar]
  30. Jhingran A, Kasahara S, Shepardson KM, Junecko BA, Heung LJ. 30.  et al. 2015. Compartment-specific and sequential role of MyD88 and CARD9 in chemokine induction and innate defense during respiratory fungal infection. PLOS Pathog 11:e1004589 [Google Scholar]
  31. Mehrad B, Strieter RM, Moore TA, Tsai WC, Lira SA, Standiford TJ. 31.  1999. CXC chemokine receptor-2 ligands are necessary components of neutrophil-mediated host defense in invasive pulmonary aspergillosis. J. Immunol. 163:6086–94 [Google Scholar]
  32. Caffrey AK, Lehmann MM, Zickovich JM, Espinosa V, Shepardson KM. 32.  et al. 2015. IL-1α signaling is critical for leukocyte recruitment after pulmonary Aspergillus fumigatus challenge. PLOS Pathog 11:e1004625 [Google Scholar]
  33. Gazendam RP, van Hamme JL, Tool AT, Hoogenboezem M, van den Berg JM. 33.  et al. 2016. Human neutrophils use different mechanisms to kill Aspergillus fumigatus conidia and hyphae: evidence from phagocyte defects. J. Immunol. 196:1272–83 [Google Scholar]
  34. Gazendam RP, van Hamme JL, Tool AT, van Houdt M, Verkuijlen PJ. 34.  et al. 2014. Two independent killing mechanisms of Candida albicans by human neutrophils: evidence from innate immunity defects. Blood 124:590–97 [Google Scholar]
  35. Zarember KA, Sugui JA, Chang YC, Kwon-Chung KJ, Gallin JI. 35.  2007. Human polymorphonuclear leukocytes inhibit Aspergillus fumigatus conidial growth by lactoferrin-mediated iron depletion. J. Immunol. 178:6367–73 [Google Scholar]
  36. Branzk N, Lubojemska A, Hardison SE, Wang Q, Gutierrez MG. 36.  et al. 2014. Neutrophils sense microbe size and selectively release neutrophil extracellular traps in response to large pathogens. Nat. Immunol. 15:1017–25 [Google Scholar]
  37. Clark HL, Jhingran A, Sun Y, Vareechon C, de Jesus Carrion S. 37.  et al. 2016. Zinc and manganese chelation by neutrophil S100A8/A9 (calprotectin) limits extracellular Aspergillus fumigatus hyphal growth and corneal infection. J. Immunol. 196:336–44 [Google Scholar]
  38. Urban CF, Reichard U, Brinkmann V, Zychlinsky A. 38.  2006. Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms. Cell. Microbiol. 8:668–76 [Google Scholar]
  39. Garg AV, Amatya N, Chen K, Cruz JA, Grover P. 39.  et al. 2015. MCPIP1 endoribonuclease activity negatively regulates interleukin-17-mediated signaling and inflammation. Immunity 43:475–87 [Google Scholar]
  40. Lionakis MS, Fischer BG, Lim JK, Swamydas M, Wan W. 40.  et al. 2012. Chemokine receptor Ccr1 drives neutrophil-mediated kidney immunopathology and mortality in invasive candidiasis. PLOS Pathog 8:e1002865 [Google Scholar]
  41. Zwolanek F, Riedelberger M, Stolz V, Jenull S, Istel F. 41.  et al. 2014. The non-receptor tyrosine kinase Tec controls assembly and activity of the noncanonical caspase-8 inflammasome. PLOS Pathog 10:e1004525 [Google Scholar]
  42. Espinosa V, Jhingran A, Dutta O, Kasahara S, Donnelly R. 42.  et al. 2014. Inflammatory monocytes orchestrate innate antifungal immunity in the lung. PLOS Pathog 10:e1003940 [Google Scholar]
  43. Ngo LY, Kasahara S, Kumasaka DK, Knoblaugh SE, Jhingran A, Hohl TM. 43.  2014. Inflammatory monocytes mediate early and organ-specific innate defense during systemic candidiasis. J. Infect. Dis. 209:109–19 [Google Scholar]
  44. Szymczak WA, Deepe GS Jr. 44.  2009. The CCL7-CCL2-CCR2 axis regulates IL-4 production in lungs and fungal immunity. J. Immunol. 183:1964–74 [Google Scholar]
  45. Phadke AP, Akangire G, Park SJ, Lira SA, Mehrad B. 45.  2007. The role of CC chemokine receptor 6 in host defense in a model of invasive pulmonary aspergillosis. Am. J. Respir. Crit. Care Med. 175:1165–72 [Google Scholar]
  46. Sterkel AK, Lorenzini JL, Fites JS, Subramanian Vignesh K, Sullivan TD. 46.  et al. 2016. Fungal mimicry of a mammalian aminopeptidase disables innate immunity and promotes pathogenicity. Cell Host Microbe 19:361–74 [Google Scholar]
  47. Lionakis MS, Swamydas M, Fischer BG, Plantinga TS, Johnson MD. 47.  et al. 2013. CX3CR1-dependent renal macrophage survival promotes Candida control and host survival. J. Clin. Invest. 123:5035–51 [Google Scholar]
  48. Subramanian Vignesh K, Landero Figueroa JA, Porollo A, Caruso JA, Deepe GS Jr. 48.  2013. Granulocyte macrophage-colony stimulating factor induced Zn sequestration enhances macrophage superoxide and limits intracellular pathogen survival. Immunity 39:697–710 [Google Scholar]
  49. Akoumianaki T, Kyrmizi I, Valsecchi I, Gresnigt MS, Samonis G. 49.  et al. 2016. Aspergillus cell wall melanin blocks LC3-associated phagocytosis to promote pathogenicity. Cell Host Microbe 19:79–90 [Google Scholar]
  50. Cheng SC, Quintin J, Cramer RA, Shepardson KM, Saeed S. 50.  et al. 2014. mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science 345:1250684 [Google Scholar]
  51. Ramirez-Ortiz ZG, Lee CK, Wang JP, Boon L, Specht CA, Levitz SM. 51.  2011. A nonredundant role for plasmacytoid dendritic cells in host defense against the human fungal pathogen Aspergillus fumigatus. . Cell Host Microbe 9:415–24 [Google Scholar]
  52. Araujo EF, Medeiros DH, Galdino NA, Condino-Neto A, Calich VL, Loures FV. 52.  2016. Tolerogenic plasmacytoid dendritic cells control Paracoccidioides brasiliensis infection by inducting regulatory T cells in an IDO-dependent manner. PLOS Pathog 12:e1006115 [Google Scholar]
  53. Guerra ES, Lee CK, Specht CA, Yadav B, Huang H. 53.  et al. 2017. Central role of IL-23 and IL-17 producing eosinophils as immunomodulatory effector cells in acute pulmonary aspergillosis and allergic asthma. PLOS Pathog 13:e1006175 [Google Scholar]
  54. Bär E, Whitney PG, Moor K, Sousa CR, LeibundGut-Landmann S. 54.  2014. IL-17 regulates systemic fungal immunity by controlling the functional competence of NK cells. Immunity 40:117–27 [Google Scholar]
  55. Dominguez-Andres J, Feo-Lucas L, Minguito de la Escalera M, Gonzalez L, Lopez-Bravo M, Ardavin C. 55.  2017. Inflammatory Ly6Chigh monocytes protect against candidiasis through IL-15-driven NK cell/neutrophil activation. Immunity 46:1059–72.e4 [Google Scholar]
  56. Li SS, Kyei SK, Timm-McCann M, Ogbomo H, Jones GJ. 56.  et al. 2013. The NK receptor NKp30 mediates direct fungal recognition and killing and is diminished in NK cells from HIV-infected patients. Cell Host Microbe 14:387–97 [Google Scholar]
  57. Park SJ, Hughes MA, Burdick M, Strieter RM, Mehrad B. 57.  2009. Early NK cell-derived IFN-γ is essential to host defense in neutropenic invasive aspergillosis. J. Immunol. 182:4306–12 [Google Scholar]
  58. Cohen NR, Tatituri RV, Rivera A, Watts GF, Kim EY. 58.  et al. 2011. Innate recognition of cell wall β-glucans drives invariant natural killer T cell responses against fungi. Cell Host Microbe 10:437–50 [Google Scholar]
  59. Steele C, Zheng M, Young E, Marrero L, Shellito JE, Kolls JK. 59.  2002. Increased host resistance against Pneumocystis carinii pneumonia in γδ T-cell-deficient mice: protective role of gamma interferon and CD8+ T cells. Infect. Immun. 70:5208–15 [Google Scholar]
  60. Conti HR, Peterson AC, Brane L, Huppler AR, Hernandez-Santos N. 60.  et al. 2014. Oral-resident natural Th17 cells and γδ T cells control opportunistic Candida albicans infections. J. Exp. Med. 211:2075–84 [Google Scholar]
  61. Kashem SW, Riedl MS, Yao C, Honda CN, Vulchanova L, Kaplan DH. 61.  2015. Nociceptive sensory fibers drive interleukin-23 production from CD301b+ dermal dendritic cells and drive protective cutaneous immunity. Immunity 43:515–26 [Google Scholar]
  62. St. Leger AJ, Desai JV, Drummond RA, Kugadas A, Almaghrabi F. 62.  et al. 2017. An ocular commensal protects against corneal infection by driving an interleukin-17 response from mucosal γδ T cells. Immunity 47:148–58.e5 [Google Scholar]
  63. Liu H, Lee MJ, Solis NV, Phan QT, Swidergall M. 63.  et al. 2016. Aspergillus fumigatus CalA binds to integrin α5β1 and mediates host cell invasion. Nat. Microbiol. 2:16211 [Google Scholar]
  64. Phan QT, Myers CL, Fu Y, Sheppard DC, Yeaman MR. 64.  et al. 2007. Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells. PLOS Biol 5:e64 [Google Scholar]
  65. Moyes DL, Wilson D, Richardson JP, Mogavero S, Tang SX. 65.  et al. 2016. Candidalysin is a fungal peptide toxin critical for mucosal infection. Nature 532:64–68 [Google Scholar]
  66. Altmeier S, Toska A, Sparber F, Teijeira A, Halin C, LeibundGut-Landmann S. 66.  2016. IL-1 coordinates the neutrophil response to C. albicans in the oral mucosa. PLOS Pathog 12:e1005882 [Google Scholar]
  67. Gebremariam T, Lin L, Liu M, Kontoyiannis DP, French S. 67.  et al. 2016. Bicarbonate correction of ketoacidosis alters host-pathogen interactions and alleviates mucormycosis. J. Clin. Investig. 126:2280–94 [Google Scholar]
  68. Wuthrich M, Deepe GS Jr, Klein B. 68.  2012. Adaptive immunity to fungi. Annu. Rev. Immunol. 30:115–48 [Google Scholar]
  69. Huang H, Ostroff GR, Lee CK, Agarwal S, Ram S. 69.  et al. 2012. Relative contributions of Dectin-1 and complement to immune responses to particulate β-glucans. J. Immunol. 189:312–17 [Google Scholar]
  70. Zielinski CE, Mele F, Aschenbrenner D, Jarrossay D, Ronchi F. 70.  et al. 2012. Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1β. Nature 484:514–18 [Google Scholar]
  71. Eddens T, Elsegeiny W, Luz Garcia-Hernadez M, Castillo P, Trevejo-Nunez G. 71.  et al. 2017. Pneumocystis-driven inducible bronchus-associated lymphoid tissue formation requires Th2 and Th17 immunity. Cell Rep 18:3078–90 [Google Scholar]
  72. Zelante T, Iannitti R, De Luca A, Romani L. 72.  2011. IL-22 in antifungal immunity. Eur. J. Immunol. 41:270–75 [Google Scholar]
  73. Araujo EF, Medeiros DH, Galdino NA, Condino-Neto A, Calich VL, Loures FV. 73.  2016. Tolerogenic plasmacytoid dendritic cells control Paracoccidioides brasiliensis infection by inducting regulatory T cells in an IDO-dependent manner. PLOS Pathog 12:e1006115 [Google Scholar]
  74. Ochs HD, Gambineri E, Torgerson TR. 74.  2007. IPEX, FOXP3 and regulatory T-cells: a model for autoimmunity. Immunol. Res. 38:112–21 [Google Scholar]
  75. Bystrom J, Taher TE, Muhyaddin MS, Clanchy FI, Mangat P. 75.  et al. 2015. Harnessing the therapeutic potential of Th17 cells. Mediat. Inflamm. 2015:205156 [Google Scholar]
  76. De Luca A Zelante T, D'Angelo C, Zagarella S, Fallarino F. 76.  et al. 2010. IL-22 defines a novel immune pathway of antifungal resistance. Mucosal Immunol 3:361–73 [Google Scholar]
  77. Walkovich K, Vander Lugt M. 77.  2017. ZAP70-related combined immunodeficiency. GeneReviews, updated June 8. Univ. Wash., Seattle, Wash.
  78. Nanjappa SG, McDermott AJ, Fites JS, Galles K, Wuthrich M. 78.  et al. 2017. Antifungal Tc17 cells are durable and stable, persisting as long-lasting vaccine memory without plasticity towards IFNγ cells. PLOS Pathog 13:e1006356 [Google Scholar]
  79. Casadevall A, Pirofski LA. 79.  2012. Immunoglobulins in defense, pathogenesis, and therapy of fungal diseases. Cell Host Microbe 11:447–56 [Google Scholar]
  80. Nabavi N, Murphy JW. 80.  1986. Antibody-dependent natural killer cell-mediated growth inhibition of Cryptococcus neoformans. . Infect. Immun. 51:556–62 [Google Scholar]
  81. Torosantucci A, Bromuro C, Chiani P, De Bernardis F, Berti F. 81.  et al. 2005. A novel glyco-conjugate vaccine against fungal pathogens. J. Exp. Med. 202:597–606 [Google Scholar]
  82. McClelland EE, Nicola AM, Prados-Rosales R, Casadevall A. 82.  2010. Ab binding alters gene expression in Cryptococcus neoformans and directly modulates fungal metabolism. J. Clin. Investig. 120:1355–61 [Google Scholar]
  83. Bowen A, Wear MP, Cordero RJB, Oscarson S, Casadevall A. 83.  2017. A monoclonal antibody to Cryptococcus neoformans glucuronoxylomannan manifests hydrolytic activity for both peptides and polysaccharides. J. Biol. Chem. 292:417–34 [Google Scholar]
  84. van Spriel AB, Sofi M, Gartlan KH, van der Schaaf A, Verschueren I. 84.  et al. 2009. The tetraspanin protein CD37 regulates IgA responses and anti-fungal immunity. PLOS Pathog 5:e1000338 [Google Scholar]
  85. Rapaka RR, Ricks DM, Alcorn JF, Chen K, Khader SA. 85.  et al. 2010. Conserved natural IgM antibodies mediate innate and adaptive immunity against the opportunistic fungus Pneumocystis murina. . J. Exp. Med. 207:2907–19 [Google Scholar]
  86. Ahn IE, Jerussi T, Farooqui M, Tian X, Wiestner A, Gea-Banacloche J. 86.  2016. Atypical Pneumocystis jirovecii pneumonia in previously untreated patients with CLL on single-agent ibrutinib. Blood 128:1940–43 [Google Scholar]
  87. Boisson B, Wang C, Pedergnana V, Wu L, Cypowyj S. 87.  et al. 2013. An ACT1 mutation selectively abolishes interleukin-17 responses in humans with chronic mucocutaneous candidiasis. Immunity 39:676–86 [Google Scholar]
  88. Levy R, Okada S, Beziat V, Moriya K, Liu C. 88.  et al. 2016. Genetic, immunological, and clinical features of patients with bacterial and fungal infections due to inherited IL-17RA deficiency. PNAS 113:E8277–85 [Google Scholar]
  89. Ling Y, Cypowyj S, Aytekin C, Galicchio M, Camcioglu Y. 89.  et al. 2015. Inherited IL-17RC deficiency in patients with chronic mucocutaneous candidiasis. J. Exp. Med. 212:619–31 [Google Scholar]
  90. Lionakis MS, Netea MG, Holland SM. 90.  2014. Mendelian genetics of human susceptibility to fungal infection. Cold Spring Harb. Perspect. Med. 4:a019638 [Google Scholar]
  91. Milner JD, Brenchley JM, Laurence A, Freeman AF, Hill BJ. 91.  et al. 2008. Impaired TH17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 452:773–76 [Google Scholar]
  92. Okada S, Markle JG, Deenick EK, Mele F, Averbuch D. 92.  et al. 2015. Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations. Science 349:606–13 [Google Scholar]
  93. Toubiana J, Okada S, Hiller J, Oleastro M, Lagos Gomez M. 93.  et al. for Int. STAT1 Gain Funct. Stud. Group 2016. Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype. Blood 127:3154–64 [Google Scholar]
  94. van de Veerdonk FL, Plantinga TS, Hoischen A, Smeekens SP, Joosten LA. 94.  et al. 2011. STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis. N. Engl. J. Med. 365:54–61 [Google Scholar]
  95. Zhang Y, Ma CA, Lawrence MG, Break TJ, O'Connell MP. 95.  et al. 2017. PD-L1 up-regulation restrains Th17 cell differentiation in STAT3 loss- and STAT1 gain-of-function patients. J. Exp. Med. 214:2523 [Google Scholar]
  96. Weinacht KG, Charbonnier LM, Alroqi F, Plant A, Qiao Q. 96.  et al. 2017. Ruxolitinib reverses dysregulated T helper cell responses and controls autoimmunity caused by a novel signal transducer and activator of transcription 1 (STAT1) gain-of-function mutation. J. Allergy Clin. Immunol. 139:1629–40.e2 [Google Scholar]
  97. Ferre EM, Rose SR, Rosenzweig SD, Burbelo PD, Romito KR. 97.  et al. 2016. Redefined clinical features and diagnostic criteria in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. JCI Insight 1:e88782 [Google Scholar]
  98. Puel A, Doffinger R, Natividad A, Chrabieh M, Barcenas-Morales G. 98.  et al. 2010. Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J. Exp. Med. 207:291–97 [Google Scholar]
  99. Shlezinger N, Irmer H, Dhingra S, Beattie SR, Cramer RA. 99.  et al. 2017. Sterilizing immunity in the lung relies on targeting fungal apoptosis-like programmed cell death. Science 357:1037–41 [Google Scholar]
  100. Kuhns DB, Alvord WG, Heller T, Feld JJ, Pike KM. 100.  et al. 2010. Residual NADPH oxidase and survival in chronic granulomatous disease. N. Engl. J. Med. 363:2600–10 [Google Scholar]
  101. Bianchi M, Hakkim A, Brinkmann V, Siler U, Seger RA. 101.  et al. 2009. Restoration of NET formation by gene therapy in CGD controls aspergillosis. Blood 114:2619–22 [Google Scholar]
  102. 102. Int. Chronic Granulomatous Dis. Coop. Study Group. 1991. A controlled trial of interferon gamma to prevent infection in chronic granulomatous disease. N. Engl. J. Med. 324:509–16 [Google Scholar]
  103. Dalgic B, Bukulmez A, Sari S. 103.  2011. Pyogenic liver abscess and peritonitis due to Rhizopus oryzae in a child with Papillon-Lefevre syndrome. Eur. J. Pediatr. 170:803–5 [Google Scholar]
  104. Swamydas M, Gao JL, Break TJ, Johnson MD, Jaeger M. 104.  et al. 2016. CXCR1-mediated neutrophil degranulation and fungal killing promote Candida clearance and host survival. Sci. Transl. Med. 8:322ra10 [Google Scholar]
  105. Wirnsberger G, Zwolanek F, Stadlmann J, Tortola L, Liu SW. 105.  et al. 2014. Jagunal homolog 1 is a critical regulator of neutrophil function in fungal host defense. Nat. Genet. 46:1028–33 [Google Scholar]
  106. Plantinga TS, Johnson MD, Scott WK, van de Vosse E, Velez Edwards DR. 106.  et al. 2012. Toll-like receptor 1 polymorphisms increase susceptibility to candidemia. J. Infect. Dis. 205:934–43 [Google Scholar]
  107. Picard C, Casanova JL, Puel A. 107.  2011. Infectious diseases in patients with IRAK-4, MyD88, NEMO, or IκBα deficiency. Clin. Microbiol. Rev. 24:490–97 [Google Scholar]
  108. Rosenfeld SI, Kelly ME, Leddy JP. 108.  1976. Hereditary deficiency of the fifth component of complement in man: I. Clinical, immunochemical, and family studies. J. Clin. Investig. 57:1626–34 [Google Scholar]
  109. Glocker EO, Hennigs A, Nabavi M, Schaffer AA, Woellner C. 109.  et al. 2009. A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N. Engl. J. Med. 361:1727–35 [Google Scholar]
  110. Rieber N, Gazendam RP, Freeman AF, Hsu AP, Collar AL. 110.  et al. 2016. Extrapulmonary Aspergillus infection in patients with CARD9 deficiency. JCI Insight 1:e89890 [Google Scholar]
  111. Lanternier F, Barbati E, Meinzer U, Liu L, Pedergnana V. 111.  et al. 2015. Inherited CARD9 deficiency in 2 unrelated patients with invasive Exophiala infection. J. Infect. Dis. 211:1241–50 [Google Scholar]
  112. Lanternier F, Pathan S, Vincent QB, Liu L, Cypowyj S. 112.  et al. 2013. Deep dermatophytosis and inherited CARD9 deficiency. N. Engl. J. Med. 369:1704–14 [Google Scholar]
  113. Drummond RA, Collar AL, Swamydas M, Rodriguez CA, Lim JK. 113.  et al. 2015. CARD9-dependent neutrophil recruitment protects against fungal invasion of the central nervous system. PLOS Pathog 11:e1005293 [Google Scholar]
  114. Drewniak A, Gazendam RP, Tool AT, van Houdt M, Jansen MH. 114.  et al. 2013. Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency. Blood 121:2385–92 [Google Scholar]
  115. Gavino C, Hamel N, Zeng JB, Legault C, Guiot MC. 115.  et al. 2016. Impaired RASGRF1/ERK-mediated GM-CSF response characterizes CARD9 deficiency in French-Canadians. J. Allergy Clin. Immunol. 137:1178–88.e7 [Google Scholar]
  116. Browne SK, Burbelo PD, Chetchotisakd P, Suputtamongkol Y, Kiertiburanakul S. 116.  et al. 2012. Adult-onset immunodeficiency in Thailand and Taiwan. N. Engl. J. Med. 367:725–34 [Google Scholar]
  117. Saijo T, Chen J, Chen SC, Rosen LB, Yi J. 117.  et al. 2014. Anti-granulocyte-macrophage colony-stimulating factor autoantibodies are a risk factor for central nervous system infection by Cryptococcus gattii in otherwise immunocompetent patients. mBio 5:e00912-14 [Google Scholar]
  118. Seitz AE, Prevots DR, Holland SM. 118.  2012. Hospitalizations associated with disseminated coccidioidomycosis, Arizona and California, USA. Emerg. Infect. Dis. 18:1476–79 [Google Scholar]
  119. Loose DS, Stover EP, Restrepo A, Stevens DA, Feldman D. 119.  1983. Estradiol binds to a receptor-like cytosol binding protein and initiates a biological response in Paracoccidioides brasiliensis. . PNAS 80:7659–63 [Google Scholar]
  120. Rajasingham R, Smith RM, Park BJ, Jarvis JN, Govender NP. 120.  et al. 2017. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect. Dis. 17:873–81 [Google Scholar]
  121. Goupil M, Cousineau-Cote V, Aumont F, Senechal S, Gaboury L. 121.  et al. 2014. Defective IL-17- and IL-22-dependent mucosal host response to Candida albicans determines susceptibility to oral candidiasis in mice expressing the HIV-1 transgene. BMC Immunol 15:49 [Google Scholar]
  122. Pirotta MV, Garland SM. 122.  2006. Genital Candida species detected in samples from women in Melbourne, Australia, before and after treatment with antibiotics. J. Clin. Microbiol. 44:3213–17 [Google Scholar]
  123. Zelante T, Iannitti RG, Cunha C, De Luca A, Giovannini G. 123.  et al. 2013. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 39:372–85 [Google Scholar]
  124. Jarvis JN, Casazza JP, Stone HH, Meintjes G, Lawn SD. 124.  et al. 2013. The phenotype of the Cryptococcus-specific CD4+ memory T-cell response is associated with disease severity and outcome in HIV-associated cryptococcal meningitis. J. Infect. Dis. 207:1817–28 [Google Scholar]
  125. Jarvis JN, Meintjes G, Bicanic T, Buffa V, Hogan L. 125.  et al. 2015. Cerebrospinal fluid cytokine profiles predict risk of early mortality and immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis. PLOS Pathog 11:e1004754 [Google Scholar]
  126. Siddiqui AA, Brouwer AE, Wuthiekanun V, Jaffar S, Shattock R. 126.  et al. 2005. IFN-gamma at the site of infection determines rate of clearance of infection in cryptococcal meningitis. J. Immunol. 174:1746–50 [Google Scholar]
  127. Jarvis JN, Meintjes G, Rebe K, Williams GN, Bicanic T. 127.  et al. 2012. Adjunctive interferon-gamma immunotherapy for the treatment of HIV-associated cryptococcal meningitis: a randomized controlled trial. AIDS 26:1105–13 [Google Scholar]
  128. Antonelli LR, Mahnke Y, Hodge JN, Porter BO, Barber DL. 128.  et al. 2010. Elevated frequencies of highly activated CD4+ T cells in HIV+ patients developing immune reconstitution inflammatory syndrome. Blood 116:3818–27 [Google Scholar]
  129. Barber DL, Mayer-Barber KD, Antonelli LR, Wilson MS, White S. 129.  et al. 2010. Th1-driven immune reconstitution disease in Mycobacterium avium-infected mice. Blood 116:3485–93 [Google Scholar]
  130. Eschke M, Piehler D, Schulze B, Richter T, Grahnert A. 130.  et al. 2015. A novel experimental model of Cryptococcus neoformans-related immune reconstitution inflammatory syndrome (IRIS) provides insights into pathogenesis. Eur. J. Immunol. 45:3339–50 [Google Scholar]
  131. Fukuda T, Boeckh M, Carter RA, Sandmaier BM, Maris MB. 131.  et al. 2003. Risks and outcomes of invasive fungal infections in recipients of allogeneic hematopoietic stem cell transplants after nonmyeloablative conditioning. Blood 102:827–33 [Google Scholar]
  132. Bodey GP, Buckley M, Sathe YS, Freireich EJ. 132.  1966. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann. Intern. Med. 64:328–40 [Google Scholar]
  133. Fan D, Coughlin LA, Neubauer MM, Kim J, Kim MS. 133.  et al. 2015. Activation of HIF-1α and LL-37 by commensal bacteria inhibits Candida albicans colonization. Nat. Med. 21:808–14 [Google Scholar]
  134. Koh AY, Kohler JR, Coggshall KT, Van Rooijen N, Pier GB. 134.  2008. Mucosal damage and neutropenia are required for Candida albicans dissemination. PLOS Pathog 4:e35 [Google Scholar]
  135. Palchaudhuri R, Saez B, Hoggatt J, Schajnovitz A, Sykes DB. 135.  et al. 2016. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat. Biotechnol. 34:738–45 [Google Scholar]
  136. Price TH, Boeckh M, Harrison RW, McCullough J, Ness PM. 136.  et al. 2015. Efficacy of transfusion with granulocytes from G-CSF/dexamethasone-treated donors in neutropenic patients with infection. Blood 126:2153–61 [Google Scholar]
  137. Baistrocchi SR, Lee MJ, Lehoux M, Ralph B, Snarr BD. 137.  et al. 2017. Posaconazole-loaded leukocytes as a novel treatment strategy targeting invasive pulmonary aspergillosis. J. Infect. Dis. 215:1734–41 [Google Scholar]
  138. Wan L, Zhang Y, Lai Y, Jiang M, Song Y. 138.  et al. 2015. Effect of granulocyte-macrophage colony-stimulating factor on prevention and treatment of invasive fungal disease in recipients of allogeneic stem-cell transplantation: a prospective multicenter randomized phase IV trial. J. Clin. Oncol. 33:3999–4006 [Google Scholar]
  139. Kandalla PK, Sarrazin S, Molawi K, Berruyer C, Redelberger D. 139.  et al. 2016. M-CSF improves protection against bacterial and fungal infections after hematopoietic stem/progenitor cell transplantation. J. Exp. Med. 213:2269–79 [Google Scholar]
  140. Lionakis MS, Kontoyiannis DP. 140.  2003. Glucocorticoids and invasive fungal infections. Lancet 362:1828–38 [Google Scholar]
  141. van de Veerdonk FL, Kolwijck E, Lestrade PPA, Hodiamont CJ, Rijnders BJA. 141.  et al.; Dutch Mycoses Study Group 2017. Influenza-associated aspergillosis in critically ill patients. Am. J. Respir. Crit. Care Med. 196:524–27 [Google Scholar]
  142. Bochud PY, Chien JW, Marr KA, Leisenring WM, Upton A. 142.  et al. 2008. Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation. N. Engl. J. Med. 359:1766–77 [Google Scholar]
  143. Fisher CE, Hohl TM, Fan W, Storer BE, Levine DM. 143.  et al. 2017. Validation of single nucleotide polymorphisms in invasive aspergillosis following hematopoietic cell transplantation. Blood 129:2693–701 [Google Scholar]
  144. Cunha C, Aversa F, Lacerda JF, Busca A, Kurzai O. 144.  et al. 2014. Genetic PTX3 deficiency and aspergillosis in stem-cell transplantation. N. Engl. J. Med. 370:421–32 [Google Scholar]
  145. Pappas PG, Alexander BD, Andes DR, Hadley S, Kauffman CA. 145.  et al. 2010. Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin. Infect. Dis. 50:1101–11 [Google Scholar]
  146. Greenblatt MB, Aliprantis A, Hu B, Glimcher LH. 146.  2010. Calcineurin regulates innate antifungal immunity in neutrophils. J. Exp. Med. 207:923–31 [Google Scholar]
  147. Singh N, Alexander BD, Lortholary O, Dromer F, Gupta KL. 147.  et al.; Cryptococcal Collab. Transpl. Study Group 2007. Cryptococcus neoformans in organ transplant recipients: impact of calcineurin-inhibitor agents on mortality. J. Infect. Dis. 195:756–64 [Google Scholar]
  148. Tsiodras S, Samonis G, Boumpas DT, Kontoyiannis DP. 148.  2008. Fungal infections complicating tumor necrosis factor alpha blockade therapy. Mayo Clin. Proc. 83:181–94 [Google Scholar]
  149. Allendoerfer R, Deepe GS Jr. 149.  2000. Regulation of infection with Histoplasma capsulatum by TNFR1 and -2. J. Immunol. 165:2657–64 [Google Scholar]
  150. Furst DE, Wallis R, Broder M, Beenhouwer DO. 150.  2006. Tumor necrosis factor antagonists: different kinetics and/or mechanisms of action may explain differences in the risk for developing granulomatous infection. Semin. Arthritis Rheum. 36:159–67 [Google Scholar]
  151. Lebwohl M, Strober B, Menter A, Gordon K, Weglowska J. 151.  et al. 2015. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N. Engl. J. Med. 373:1318–28 [Google Scholar]
  152. Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P. 152.  et al. 2015. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N. Engl. J. Med. 373:1329–39 [Google Scholar]
  153. Papp KA, Blauvelt A, Bukhalo M, Gooderham M, Krueger JG. 153.  et al. 2017. Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis. N. Engl. J. Med. 376:1551–60 [Google Scholar]
  154. Kyriakidis I, Tragiannidis A, Zündorf I, Groll AH. 154.  2017. Invasive fungal infections in paediatric patients treated with macromolecular immunomodulators other than tumour necrosis alpha inhibitors. Mycoses 60:493–507 [Google Scholar]
  155. Romani L, Mencacci A, Cenci E, Spaccapelo R, Toniatti C. 155.  et al. 1996. Impaired neutrophil response and CD4+ T helper cell 1 development in interleukin 6-deficient mice infected with Candida albicans. . J. Exp. Med. 183:1345–55 [Google Scholar]
  156. Osterborg A, Mellstedt H, Keating M. 156.  2002. Clinical effects of alemtuzumab (Campath-1H) in B-cell chronic lymphocytic leukemia. Med. Oncol. 19:Suppl.S21–26 [Google Scholar]
  157. Elsegeiny W, Eddens T, Chen K, Kolls JK. 157.  2015. Anti-CD20 antibody therapy and susceptibility to Pneumocystis pneumonia. Infect. Immun. 83:2043–52 [Google Scholar]
  158. Martin-Garrido I, Carmona EM, Specks U, Limper AH. 158.  2013. Pneumocystis pneumonia in patients treated with rituximab. Chest 144:258–65 [Google Scholar]
  159. Moodley D, Yoshida H, Mostafavi S, Asinovski N, Ortiz-Lopez A. 159.  et al. 2016. Network pharmacology of JAK inhibitors. PNAS 113:9852–57 [Google Scholar]
  160. Lionakis MS, Dunleavy K, Roschewski M, Widemann BC, Butman JA. 160.  et al. 2017. Inhibition of B cell receptor signaling by ibrutinib in primary CNS lymphoma. Cancer Cell 31:833–43.e5 [Google Scholar]
  161. Cheah CY, Fowler NH. 161.  2016. Idelalisib in the management of lymphoma. Blood 128:331–36 [Google Scholar]
  162. Valenzuela RM, Pula JH, Garwacki D, Cotter J, Kattah JC. 162.  2014. Cryptococcal meningitis in a multiple sclerosis patient taking natalizumab. J. Neurol. Sci. 340:109–11 [Google Scholar]
  163. Williams J, Lim R, Tambyah P. 163.  2007. Invasive aspergillosis associated with bevacizumab, a vascular endothelial growth factor inhibitor. Int. J. Infect. Dis. 11:549–50 [Google Scholar]
  164. Sillaber C, Herrmann H, Bennett K, Rix U, Baumgartner C. 164.  et al. 2009. Immunosuppression and atypical infections in CML patients treated with dasatinib at 140 mg daily. Eur. J. Clin. Investig. 39:1098–109 [Google Scholar]
  165. Chang KC, Burnham CA, Compton SM, Rasche DP, Mazuski RJ. 165.  et al. 2013. Blockade of the negative co-stimulatory molecules PD-1 and CTLA-4 improves survival in primary and secondary fungal sepsis. Crit. Care 17:R85 [Google Scholar]
  166. Lazar-Molnar E, Gacser A, Freeman GJ, Almo SC, Nathenson SG, Nosanchuk JD. 166.  2008. The PD-1/PD-L costimulatory pathway critically affects host resistance to the pathogenic fungus Histoplasma capsulatum. . PNAS 105:2658–63 [Google Scholar]
  167. Grimaldi D, Pradier O, Hotchkiss RS, Vincent JL. 167.  2017. Nivolumab plus interferon-gamma in the treatment of intractable mucormycosis. Lancet Infect. Dis. 17:18 [Google Scholar]
  168. Levitz SM, Golenbock DT. 168.  2012. Beyond empiricism: informing vaccine development through innate immunity research. Cell 148:1284–92 [Google Scholar]
  169. Armstrong-James D, Brown GD, Netea MG, Zelante T, Gresnigt MS. 169.  et al. 2017. Immunotherapeutic approaches to treatment of fungal diseases. Lancet Infect. Dis. 17:e393–402 [Google Scholar]
  170. Stevens DA, Clemons KV, Liu M. 170.  2011. Developing a vaccine against aspergillosis. Med. Mycol. 49:Suppl. 1S170–76 [Google Scholar]
  171. Wuthrich M, Brandhorst TT, Sullivan TD, Filutowicz H, Sterkel A. 171.  et al. 2015. Calnexin induces expansion of antigen-specific CD4+ T cells that confer immunity to fungal ascomycetes via conserved epitopes. Cell Host Microbe 17:452–65 [Google Scholar]
  172. Yeaman MR, Filler SG, Schmidt CS, Ibrahim AS, Edwards JE, Hennessey JP Jr. 172.  2014. Applying convergent immunity to innovative vaccines targeting Staphylococcus aureus. . Front. Immunol. 5:463 [Google Scholar]
  173. Nanjappa SG, Heninger E, Wuthrich M, Gasper DJ, Klein BS. 173.  2012. Tc17 cells mediate vaccine immunity against lethal fungal pneumonia in immune deficient hosts lacking CD4+ T cells. PLOS Pathog 8:e1002771 [Google Scholar]
  174. Wuthrich M, Filutowicz HI, Warner T, Deepe GS Jr, Klein BS. 174.  2003. Vaccine immunity to pathogenic fungi overcomes the requirement for CD4 help in exogenous antigen presentation to CD8+ T cells: implications for vaccine development in immune-deficient hosts. J. Exp. Med. 197:1405–16 [Google Scholar]
  175. Narra HP, Shubitz LF, Mandel MA, Trinh HT, Griffin K. 175.  et al. 2016. A Coccidioides posadasii CPS1 deletion mutant is avirulent and protects mice from lethal infection. Infect. Immun. 84:3007–16 [Google Scholar]
  176. Upadhya R, Lam WC, Maybruck B, Specht CA, Levitz SM, Lodge JK. 176.  2016. Induction of protective immunity to cryptococcal infection in mice by a heat-killed, chitosan-deficient strain of Cryptococcus neoformans. . mBio 7:e00547–16 [Google Scholar]
  177. Pappagianis D. 177. , Val. Fever Study Group. 1993. Evaluation of the protective efficacy of the killed Coccidioides immitis spherule vaccine in humans. Am. Rev. Respir. Dis. 148:656–60 [Google Scholar]
  178. Nanjappa SG, Klein BS. 178.  2014. Vaccine immunity against fungal infections. Curr. Opin. Immunol. 28:27–33 [Google Scholar]
  179. Santos E, Levitz SM. 179.  2014. Fungal vaccines and immunotherapeutics. Cold Spring Harb. Perspect. Med. 4:a019711 [Google Scholar]
  180. Levitz SM, Huang H, Ostroff GR, Specht CA. 180.  2015. Exploiting fungal cell wall components in vaccines. Semin. Immunopathol. 37:199–207 [Google Scholar]
  181. Huang H, Ostroff GR, Lee CK, Specht CA, Levitz SM. 181.  2010. Robust stimulation of humoral and cellular immune responses following vaccination with antigen-loaded β-glucan particles. mBio 1:e00164–10 [Google Scholar]
  182. Huang H, Ostroff GR, Lee CK, Specht CA, Levitz SM. 182.  2013. Characterization and optimization of the glucan particle-based vaccine platform. Clin. Vaccine Immunol. 20:1585–91 [Google Scholar]
  183. Specht CA, Lee CK, Huang H, Tipper DJ, Shen ZT. 183.  et al. 2015. Protection against experimental cryptococcosis following vaccination with glucan particles containing Cryptococcus alkaline extracts. mBio 6:e01905–15 [Google Scholar]
  184. King TH, Guo Z, Hermreck M, Bellgrau D, Rodell TC. 184.  2016. Construction and immunogenicity testing of whole recombinant yeast-based T-cell vaccines. Vaccine Design: Methods and Protocols, Vol. 2: Vaccines for Veterinary Diseases S Thomas 529–45 New York: Springer [Google Scholar]
  185. Levitz SM, Specht CA. 185.  2006. The molecular basis for the immunogenicity of Cryptococcus neoformans mannoproteins. FEMS Yeast Res 6:513–24 [Google Scholar]
  186. Sancho D, Reis e Sousa C. 186.  2012. Signaling by myeloid C-type lectin receptors in immunity and homeostasis. Annu. Rev. Immunol. 30:491–529 [Google Scholar]
  187. Hardison SE, Brown GD. 187.  2012. C-type lectin receptors orchestrate antifungal immunity. Nat. Immunol. 13:817–22 [Google Scholar]
  188. Specht CA, Nong S, Dan JM, Lee CK, Levitz SM. 188.  2007. Contribution of glycosylation to T cell responses stimulated by recombinant Cryptococcus neoformans mannoprotein. J. Infect. Dis. 196:796–800 [Google Scholar]
  189. Lam JS, Mansour MK, Specht CA, Levitz SM. 189.  2005. A model vaccine exploiting fungal mannosylation to increase antigen immunogenicity. J. Immunol. 175:7496–503 [Google Scholar]
  190. Irache JM, Salman HH, Gamazo C, Espuelas S. 190.  2008. Mannose-targeted systems for the delivery of therapeutics. Expert Opin. Drug Deliv. 5:703–24 [Google Scholar]
  191. He L-Z, Weidlick J, Sisson C, Marsh HC, Keler T. 191.  2015. Toll-like receptor agonists shape the immune responses to a mannose receptor-targeted cancer vaccine. Cell Mol. Immunol. 12:719–28 [Google Scholar]
  192. Dan JM, Wang JP, Lee CK, Levitz SM. 192.  2008. Cooperative stimulation of dendritic cells by Cryptococcus neoformans mannoproteins and CpG oligodeoxynucleotides. PLOS ONE 3:e2046 [Google Scholar]
  193. Smith A, Perelman M, Hinchcliffe M. 193.  2014. Chitosan. Hum. Vaccines Immunother. 10:797–807 [Google Scholar]
  194. Bueter CL, Lee CK, Wang JP, Ostroff GR, Specht CA, Levitz SM. 194.  2014. Spectrum and mechanisms of inflammasome activation by chitosan. J. Immunol. 192:5943–51 [Google Scholar]
  195. Larsen RA, Pappas PG, Perfect J, Aberg JA, Casadevall A. 195.  et al. 2005. Phase I evaluation of the safety and pharmacokinetics of murine-derived anticryptococcal antibody 18B7 in subjects with treated cryptococcal meningitis. Antimicrob. Agents Chemother. 49:952–58 [Google Scholar]
  196. Cywes-Bentley C, Skurnik D, Zaidi T, Roux D, Deoliveira RB. 196.  et al. 2013. Antibody to a conserved antigenic target is protective against diverse prokaryotic and eukaryotic pathogens. PNAS 110:E2209–18 [Google Scholar]
  197. Bozza S, Perruccio K, Montagnoli C, Gaziano R, Bellocchio S. 197.  et al. 2003. A dendritic cell vaccine against invasive aspergillosis in allogeneic hematopoietic transplantation. Blood 102:3807–14 [Google Scholar]
  198. Perruccio K, Tosti A, Burchielli E, Topini F, Ruggeri L. 198.  et al. 2005. Transferring functional immune responses to pathogens after haploidentical hematopoietic transplantation. Blood 106:4397–406 [Google Scholar]
  199. Stuehler C, Nowakowska J, Bernardini C, Topp MS, Battegay M. 199.  et al. 2015. Multispecific Aspergillus T cells selected by CD137 or CD154 induce protective immune responses against the most relevant mold infections. J. Infect. Dis. 211:1251–61 [Google Scholar]
  200. Kumaresan PR, Manuri PR, Albert ND, Maiti S, Singh H. 200.  et al. 2014. Bioengineering T cells to target carbohydrate to treat opportunistic fungal infection. PNAS 111:10660–65 [Google Scholar]
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