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Annual Review of Virology

Volume 8, 2021

Bacteriophages and the Immune System

Abstract

Bacteriophages—viruses that infect bacteria—are abundant within our bodies, but their significance to human health is only beginning to be explored. Here, we synthesize what is currently known about our phageome and its interactions with the immune system. We first review how phages indirectly affect immunity via bacterial expression of phage-encoded proteins. We next review how phages directly influence innate immunity and bacterial clearance. Finally, we discuss adaptive immunity against phages and its implications for phage/bacterial interactions. In light of these data, we propose that our microbiome can be understood as an interconnected network of bacteria, bacteriophages, and human cells and that the stability of these tri-kingdom interactions may be important for maintaining our immunologic and metabolic health. Conversely, the disruption of this balance, through exposure to exogenous phages, microbial dysbiosis, or immune dysregulation, may contribute to disease.

Keyword(s): bacteriophage, commensal, immune, microbiome, phage display, phageome
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/content/journals/10.1146/annurev-virology-091919-074551
2021-09-29
2025-04-24
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Literature Cited

  1. 1. 
    Kortright KE, Chan BK, Koff JL, Turner PE 2019. Phage therapy: a renewed approach to combat antibiotic-resistant bacteria. Cell Host Microbe 25:219–32
     [Google Scholar]
  2. 2. 
    Gordillo Altamirano FL, Barr JJ 2019. Phage therapy in the postantibiotic era. Clin. Microbiol. Rev. 32:00066-18
     [Google Scholar]
  3. 3. 
    González-Mora A, Hernández-Pérez J, Iqbal HMN, Rito-Palomares M, Benavides J 2020. Bacteriophage-based vaccines: a potent approach for antigen delivery. Vaccines 8:504
     [Google Scholar]
  4. 4. 
    Nguyen S, Baker K, Padman BS, Patwa R, Dunstan RA et al. 2017. A Bacteriophage transcytosis provides a mechanism to cross epithelial cell layers. mBio 8:6e01874-17Bacteriophage transport through cell monolayers from different origin tissues is described.
     [Google Scholar]
  5. 5. 
    Ogilvie LA, Jones BV 2015. The human gut virome: a multifaceted majority. Front. Microbiol. 6:918
     [Google Scholar]
  6. 6. 
    Oh J, Byrd AL, Park M, Kong HH, Segre JA 2016. Temporal stability of the human skin microbiome. Cell 165:4854–66
     [Google Scholar]
  7. 7. 
    da Costa AC, Moron AF, Forney LJ, Linhares IM, Sabino E et al. 2021. Identification of bacteriophages in the vagina of pregnant women: a descriptive study. BJOG 128:6976–82
     [Google Scholar]
  8. 8. 
    Tariq MA, Everest FLC, Cowley LA, De Soyza AD, Holt GS et al. 2015. A metagenomic approach to characterize temperate bacteriophage populations from Cystic Fibrosis and non-Cystic Fibrosis bronchiectasis patients. Front. Microbiol. 18:697
     [Google Scholar]
  9. 9. 
    Ren J, Ahlgren NA, Lu YY, Fuhrman JA, Sun F. 2017. VirFinder: a novel k-mer based tool for identifying viral sequences from assembled metagenomic data. Microbiome 5:169
     [Google Scholar]
  10. 10. 
    Zhang T, Breitbart M, Lee WH, Run JQ, Wei CL et al. 2006. RNA viral community in human feces: prevalence of plant pathogenic viruses. PLOS Biol. 4:1e3
     [Google Scholar]
  11. 11. 
    Roux S, Krupovic M, Daly RA, Borges AL, Nayfach S et al. 2019. Cryptic inoviruses revealed as pervasive in bacteria and archaea across Earth's biomes. Nat. Microbiol. 4:111895–906
     [Google Scholar]
  12. 12. 
    Mai-Prochnow A, Hui JGK, Kjelleberg S, Rakonjac J, McDougald D, Rice SA. 2015. Big things in small packages: the genetics of filamentous phage and effects on fitness of their host. FEMS Microbiol. Rev. 39:465–87
     [Google Scholar]
  13. 13. 
    Hoyles L, McCartney AL, Neve H, Gibson GR, Sanderson JD et al. 2014. Characterization of virus-like particles associated with the human faecal and caecal microbiota. Res. Microbiol. 165:10803–12
     [Google Scholar]
  14. 14. 
    Broecker F, Russo G, Klumpp J, Moelling K. 2017. Stable core virome despite variable microbiome after fecal transfer. Gut Microbes 8:214–20
     [Google Scholar]
  15. 15. 
    Shkoporov AN, Clooney AG, Sutton TDS, Ryan FJ, Daly KM et al. 2019. The human gut virome is highly diverse, stable, and individual specific. Cell Host Microbe 26:4527–41Longitudinal metagenomic analysis among human fecal viral samples reveals temporally stable viral communities that are individual and microbiome specific.
     [Google Scholar]
  16. 16. 
    Zuo T, Wong SH, Lam K, Lui R, Cheung K et al. 2018. Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome. Gut 67:4634–43
     [Google Scholar]
  17. 17. 
    Norman JM, Handley SA, Baldridge MT, Droit L, Liu CY et al. 2015. Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 160:3447–60
     [Google Scholar]
  18. 18. 
    Ma Y, You X, Mai G, Tokuyasu T, Liu C. 2018. A human gut phage catalog correlates the gut phageome with type 2 diabetes. Microbiome 1:624
     [Google Scholar]
  19. 19. 
    Gregory AC, Sullivan MB, Segal LN, Keller BC. 2018. Smoking is associated with quantifiable differences in the human lung DNA virome and metabolome. Respir. Res. 19:1174
     [Google Scholar]
  20. 20. 
    Shkoporov AN, Hill C. 2019. Bacteriophages of the human gut: the “known unknown” of the microbiome. Cell Host Microbe 25:2195–209
     [Google Scholar]
  21. 21. 
    Weinbauer MG. 2004. Ecology of prokaryotic viruses. FEMS Microbiol. Rev. 28:2127–81
     [Google Scholar]
  22. 22. 
    Brüssow H, Canchaya C, Hardt W-D. 2004. Phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion. Microbiol. . Mol. Biol. Rev. 68:3560–602
     [Google Scholar]
  23. 23. 
    Waldor MK, Mekalanos JJ. 1996. Lysogenic conversion by a filamentous phage encoding cholera toxin. Science 272:52701910–14
     [Google Scholar]
  24. 24. 
    Vaca Pacheco S, Garcıća González O, Paniagua Contreras GL 2006. The lom gene of bacteriophage λ is involved in Escherichia coli K12 adhesion to human buccal epithelial cells. FEMS Microbiol. Lett. 156:1129–32
     [Google Scholar]
  25. 25. 
    Bensing BA, Rubens CE, Sullam PM. 2001. Genetic loci of Streptococcus mitis that mediate binding to human platelets. Infect. Immun. 69:31373–80
     [Google Scholar]
  26. 26. 
    Stanley TL, Ellermeier CD, Slauch JM. 2000. Tissue-specific gene expression identifies a gene in the lysogenic phage Gifsy-1 that affects Salmonella enterica serovar Typhimurium survival in Peyer's patches. J. Bacteriol. 182:164406–13
     [Google Scholar]
  27. 27. 
    Hynes WL, Ferretti JJ. 1989. Sequence analysis and expression in Escherichia coli of the hyaluronidase gene of Streptococcus pyogenes bacteriophage H4489A. Infect. Immun. 57:2533–39
     [Google Scholar]
  28. 28. 
    Secor PR, Sweere JM, Michaels LA, Malkovskiy AV, Lazzareschi D et al. 2015. Filamentous bacteriophage promote biofilm assembly and function. Cell Host Microbe 18:549–59
     [Google Scholar]
  29. 29. 
    Veldkamp KE, Heezius HCJM, Verhoef J, Van Strijp JAG, Van Kessel KPM. 2000. Modulation of neutrophil chemokine receptors by Staphylococcus aureus supernate. Infect. Immun. 68:105908–13
     [Google Scholar]
  30. 30. 
    do Vale A, Cabanes D, Sousa S. 2016. Bacterial toxins as pathogen weapons against phagocytes. Front. Microbiol. 1:42
     [Google Scholar]
  31. 31. 
    Figueroa-Bossi N, Bossi L. 1999. Inducible prophages contribute to Salmonella virulence in mice. Mol. Microbiol. 33:1167–76
     [Google Scholar]
  32. 32. 
    Pasechnek A, Rabinovich L, Stadnyuk O, Azulay G, Mioduser J et al. 2020. Active lysogeny in Listeria monocytogenes is a bacteria-phage adaptive response in the mammalian environment. Cell Rep 32:4107956
     [Google Scholar]
  33. 33. 
    Ikebe T, Wada A, Inagaki Y, Sugama K, Suzuki R et al. 2002. Dissemination of the phage-associated novel superantigen gene speL in recent invasive and noninvasive Streptococcus pyogenes M3/T3 isolates in Japan. Infect. Immun. 70:63227–33
     [Google Scholar]
  34. 34. 
    Schmitt MP, Twiddy EM, Holmes RK. 1992. Purification and characterization of the diphtheria toxin repressor. PNAS 89:167576–80
     [Google Scholar]
  35. 35. 
    Schmitt MP, Holmes RK. 1991. Iron-dependent regulation of diphtheria toxin and siderophore expression by the cloned Corynebacterium diphtheriae repressor gene dtxR in C. diphtheriae C7 strains. Infect. Immun. 59:61899–904
     [Google Scholar]
  36. 36. 
    Boyd J, Oza MN, Murphy JR. 1990. Molecular cloning and DNA sequence analysis of a diphtheria tox iron-dependent regulatory element (dtxR) from Corynebacterium diphtheriae. PNAS 87:155968–72
     [Google Scholar]
  37. 37. 
    Voelker LL, Dybvig K. 1999. Sequence analysis of the Mycoplasma arthritidis bacteriophage MAV1 genome identifies the putative virulence factor. Gene 233:1–2101–7
     [Google Scholar]
  38. 38. 
    Goh S, Hussain H, Chang BJ, Emmett W, Riley TV, Mullany P 2013. Phage ϕC2 mediates transduction of Tn6215, encoding erythromycin resistance, between Clostridium difficile strains. mBio 4:6e00840-13
     [Google Scholar]
  39. 39. 
    Nezhad Fard RM, Barton MD, Heuzenroeder MW. 2011. Bacteriophage-mediated transduction of antibiotic resistance in enterococci. Lett. Appl. Microbiol. 52:6559–64
     [Google Scholar]
  40. 40. 
    Wang X, Kim Y, Ma Q, Hong SH, Pokusaeva K et al. 2010. Cryptic prophages help bacteria cope with adverse environments. Nat. Commun. 1:9147
     [Google Scholar]
  41. 41. 
    Jain R, Rivera MC, Lake JA. 1999. Horizontal gene transfer among genomes: the complexity hypothesis. PNAS 96:73801–6
     [Google Scholar]
  42. 42. 
    Gebhart D, Williams SR, Bishop-Lilly KA, Govoni GR, Willner KM et al. 2012. Novel high-molecular-weight, R-type bacteriocins of Clostridium difficile. J. Bacteriol. 194:226240–47
     [Google Scholar]
  43. 43. 
    Barr JJ, Auro R, Furlan M, Whiteson KL, Erb ML et al. 2013. Bacteriophage adhering to mucus provide a non-host-derived immunity. PNAS 110:2610771–76T4 phages are shown to interact with mammalian mucosa through capsid immunoglobulin-like domains.
     [Google Scholar]
  44. 44. 
    Fraser JS, Yu Z, Maxwell KL, Davidson AR. 2006. Ig-like domains on bacteriophages: a tale of promiscuity and deceit. J. Mol. Biol. 359:2496–507
     [Google Scholar]
  45. 45. 
    Bateman A, Eddy SR, Mesyanzhinov VV. 1997. A member of the immunoglobulin superfamily in bacteriophage T4. Virus Genes 14:2163–65
     [Google Scholar]
  46. 46. 
    Almeida GMF, Laanto E, Ashrafi R, Sundberg LR. 2019. Bacteriophage adherence to mucus mediates preventive protection against pathogenic bacteria. mBio 10:601984-19
     [Google Scholar]
  47. 47. 
    Barr JJ, Auro R, Sam-Soon N, Kassegne S, Peters G et al. 2015. Subdiffusive motion of bacteriophage in mucosal surfaces increases the frequency of bacterial encounters. PNAS 112:4413675–80
     [Google Scholar]
  48. 48. 
    Yang JY, Kim MS, Kim E, Cheon JH, Lee YS et al. 2016. Enteric viruses ameliorate gut inflammation via Toll-like receptor 3 and Toll-like receptor 7-mediated interferon-β production. Immunity 44:4889–900
     [Google Scholar]
  49. 49. 
    Gogokhia L, Buhrke K, Bell R, Casjens SR, Longman RS, Round JL. 2019. Expansion of bacteriophages is linked to aggravated intestinal inflammation and colitis. Cell Host Microbe 25:285–99Germ-free mice treated with a phage cocktail exhibit TLR9-dependent immune cell activation.
     [Google Scholar]
  50. 50. 
    Barr JJ. 2017. A bacteriophages journey through the human body. Immunol. Rev. 279:1106–22
     [Google Scholar]
  51. 51. 
    Miȩdzybrodzki R, Kłak M, Jonczyk-Matysiak E, Bubak B, Wójcik A et al. 2017. Means to facilitate the overcoming of gastric juice barrier by a therapeutic staphylococcal bacteriophage A5/80. Front. Microbiol. 8:467
     [Google Scholar]
  52. 52. 
    Duerr DM, White SJ, Schluesener HJ. 2004. Identification of peptide sequences that induce the transport of phage across the gastrointestinal mucosal barrier. J. Virol. Methods 116:2177–80
     [Google Scholar]
  53. 53. 
    Wolochow H, Hildebrand GJ, Lamanna C. 1966. Translocation of microorganisms across the intestinal wall of the rat: effect of microbial size and concentration. J. Infect. Dis. 116:4523–28
     [Google Scholar]
  54. 54. 
    Pacífico C, Hilbert M, Sofka D, Dinhopl N, Pap IJ et al. 2019. Natural occurrence of Escherichia coli-infecting bacteriophages in clinical samples. Front. Microbiol. 10:2484
     [Google Scholar]
  55. 55. 
    Hoffmann M. 1965. Animal experiments on mucosal passage and absorption viraemia of T3 phages after oral, tracheal and rectal administration. Zentralblatt Bakteriol. Parasitenkd. Infekt. Hyg. 198:4371–90
     [Google Scholar]
  56. 56. 
    Keller R, Engley FB. 1958. Fate of bacteriophage particles introduced into mice by various routes. Proc. Soc. Exp. Biol. Med. 98:3577–80
     [Google Scholar]
  57. 57. 
    Smith HW, Huggins MB. 1982. Successful treatment of experimental Escherichia coli infections in mice using phage: its general superiority over antibiotics. J. Gen. Microbiol. 128:307–10
     [Google Scholar]
  58. 58. 
    Inchley CJ. 1969. The activity of mouse Kupffer cells following intravenous injection of T4 bacteriophage. Clin. Exp. Immunol. 5:1173–87
     [Google Scholar]
  59. 59. 
    Schultz I, Neva FA. 1965. Relationship between blood clearance and viruria after intravenous injection of mice and rats with bacteriophage and poliovirus. J. Immunol. 94:6833–41
     [Google Scholar]
  60. 60. 
    Sechter I, Touitou E, Donbrow M. 1989. The influence of a non-ionic surfactant on rectal absorption of virus particles. Arch. Virol. 106:141–43
     [Google Scholar]
  61. 61. 
    Nungester WJ, Watrous RM. 1934. Accumulation of bacteriophage in spleen and liver following its intravenous inoculation. Exp. Biol. Med. 31:8901–5
     [Google Scholar]
  62. 62. 
    Geier MR, Trigg ME, Merril CR. 1973. Fate of bacteriophage lambda in non-immune germ-free mice. Nature 246:5430221–23
     [Google Scholar]
  63. 63. 
    Keller R, Zatzman M. 1956. Studies on the factors concerned in the disappearance of bacteriophage particles from the animal body. J. Immunol. 83:167–72
     [Google Scholar]
  64. 64. 
    Reynaud A, Cloastre L, Bernard J, Laveran H, Ackermann HW et al. 1992. Characteristics and diffusion in the rabbit of a phage for Escherichia coli 0103. Attempts to use this phage for therapy. Vet. Microbiol. 30:2–3203–12
     [Google Scholar]
  65. 65. 
    Guillot A, Tacke F. 2019. Liver macrophages: old dogmas and new insights. Hepatol. Commun. 3:6730–43
     [Google Scholar]
  66. 66. 
    Movita D, Kreefft K, Biesta P, van Oudenaren A, Leenen PJM et al. 2012. Kupffer cells express a unique combination of phenotypic and functional characteristics compared with splenic and peritoneal macrophages. J. Leukoc. Biol. 92:4723–33
     [Google Scholar]
  67. 67. 
    Barfoot R, Denham S, Gyure LA, Hall JG, Hobbs SM et al. 1989. Some properties of dendritic macrophages from peripheral lymph. Immunology 68:2233–39
     [Google Scholar]
  68. 68. 
    Aronow R, Danon D, Shahar A, Aronson M. 1964. Electron microscopy of endocytosis of T2-phage by cells from rabbit peritoneal exudate. J. Exp. Med. 12:5943–54
     [Google Scholar]
  69. 69. 
    Ochs HD, Davis SD, Wedgwood RJ. 1971. Immunologic responses to bacteriophage ϕX 174 in immunodeficiency diseases. J. Clin. Investig. 50:122559–68
     [Google Scholar]
  70. 70. 
    Hodyra-Stefaniak K, Miernikiewicz P, Drapała J, Drab M, Jonczyk-Matysiak E et al. 2015. Mammalian host-versus-phage immune response determines phage fate in vivo. Sci. Rep. 5:114802
     [Google Scholar]
  71. 71. 
    Srivastava AS, Chauhan DP, Carrier E. 2004. In utero detection of T7 phage after systemic administration to pregnant mice. Biotechniques 37:181–83
     [Google Scholar]
  72. 72. 
    Dubos RJ, Straus JH, Pierce C. 1943. The multiplication of bacteriophage in vivo and its protective effect against an experimental infection with Shigella dysenteriae. J. Exp. Med. 78:3161–68
     [Google Scholar]
  73. 73. 
    Ghose C, Ly M, Schwanemann LK, Shin JH, Atab K et al. 2019. The virome of cerebrospinal fluid: viruses where we once thought there were none. Front. Microbiol. 10:2061
     [Google Scholar]
  74. 74. 
    Bronte V, Pittet MJ. 2013. The spleen in local and systemic regulation of immunity. Immunity 39:806–18
     [Google Scholar]
  75. 75. 
    Bilzer M, Roggel F, Gerbes AL. 2006. Role of Kupffer cells in host defense and liver disease. Liver Int 26:101175–86
     [Google Scholar]
  76. 76. 
    Secor PR, Michaels LA, Smigiel KS, Rohani MG, Jennings LK et al. 2017. Filamentous bacteriophage produced by Pseudomonas aeruginosa alters the inflammatory response and promotes noninvasive infection in vivo. Infect. Immun. 85:1e00648-16
     [Google Scholar]
  77. 77. 
    Zaczek M, Górski A, Skaradzińska A, Łusiak-Szelachowska M, Weber-D'browska B. 2019. Phage penetration of eukaryotic cells: practical implications. Future Virol 14:745–60
     [Google Scholar]
  78. 78. 
    Dabrowska K, Opolski A, Wietrzyk J, Switala-Jelen K, Boratynski J et al. 2004. Antitumor activity of bacteriophages in murine experimental cancer models caused possibly by inhibition of β3 integrin signaling pathway. Acta Virol 48:4241–48
     [Google Scholar]
  79. 79. 
    Kim A, Shin TH, Shin SM, Pham CD, Choi DK et al. 2012. Cellular internalization mechanism and intracellular trafficking of filamentous M13 phages displaying a cell-penetrating transbody and TAT peptide. PLOS ONE 7:12e51813
     [Google Scholar]
  80. 80. 
    Tian Y, Wu M, Liu X, Liu Z, Zhou Q et al. 2015. Probing the endocytic pathways of the filamentous bacteriophage in live cells using ratiometric pH fluorescent indicator. Adv. Healthc. Mater. 4:3413–19
     [Google Scholar]
  81. 81. 
    Dedrick RM, Guerrero-Bustamante CA, Garlena RA, Russell DA, Ford K et al. 2019. Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus. Nat. Med. 25:5730–33
     [Google Scholar]
  82. 82. 
    Rabinovich L, Sigal N, Borovok I, Nir-Paz R, Herskovits AA. 2012. Prophage excision activates listeria competence genes that promote phagosomal escape and virulence. Cell 150:4792–802
     [Google Scholar]
  83. 83. 
    Manickan E, Karem KL, Rouse BT. 2017. DNA vaccines—a modern gimmick or a boon to vaccinology?. Crit. Rev. Immunol. 37:2–6483–98
     [Google Scholar]
  84. 84. 
    Bodner K, Melkonian AL, Covert MW. 2021. The enemy of my enemy: new insights regarding bacteriophage–mammalian cell interactions. Trends Microbiol 29:6528–41
     [Google Scholar]
  85. 85. 
    Hess KL, Jewell CM. 2020. Phage display as a tool for vaccine and immunotherapy development. Bioeng. Transl. Med. 5:1e10142
     [Google Scholar]
  86. 86. 
    Paludan SR, Bowie AG. 2013. Immune sensing of DNA. Immunity 38:870–80
     [Google Scholar]
  87. 87. 
    Hashiguchi S, Yamaguchi Y, Takeuchi O, Akira S, Sugimura K. 2010. Immunological basis of M13 phage vaccine: regulation under MyD88 and TLR9 signaling. Biochem. Biophys. Res. Commun. 402:119–22
     [Google Scholar]
  88. 88. 
    Kawasaki T, Kawai T. 2014. Toll-like receptor signaling pathways. Front. Immunol. 5:461
     [Google Scholar]
  89. 89. 
    Rutz M, Metzger J, Gellert T, Luppa P, Lipford GB et al. 2004. Toll-like receptor 9 binds single-stranded CpG-DNA in a sequence- and pH-dependent manner. Eur. J. Immunol. 34:92541–50
     [Google Scholar]
  90. 90. 
    Sweere JM, Van Belleghem JD, Ishak H, Bach MS, Popescu M et al. 2019. Bacteriophage trigger antiviral immunity and prevent clearance of bacterial infection. Science 363:6434eaat9691Filamentous Pf phage downregulates myeloid cell inflammation in a TLR3-dependent manner.
     [Google Scholar]
  91. 91. 
    Geier MR, Merril CR. 1972. Lambda phage transcription in human fibroblasts. Virology 47:3638–43
     [Google Scholar]
  92. 92. 
    Merril CR, Geier MR, Petricciani JC. 1971. Bacterial virus gene expression in human cells. Nature 233:5319398–400In human fibroblasts treated with lambda phage, 0.2% of total RNA was lamdba-specific at 4d.
     [Google Scholar]
  93. 93. 
    Basu R, Zhai L, Contreras A, Tumban E. 2018. Immunization with phage virus-like particles displaying Zika virus potential B-cell epitopes neutralizes Zika virus infection of monkey kidney cells. Vaccine 36:101256–64
     [Google Scholar]
  94. 94. 
    Wang L, Gao J, Lan X, Zhao H, Shang X et al. 2019. Identification of combined T-cell and B-cell reactive Echinococcus granulosus 95 antigens for the potential development of a multi-epitope vaccine. Ann. Transl. Med. 7:22652
     [Google Scholar]
  95. 95. 
    Carvalho GB, Costa LE, Lage DP, Ramos FF, Santos TTO et al. 2019. High-through identification of T cell-specific phage-exposed mimotopes using PBMCs from tegumentary leishmaniasis patients and their use as vaccine candidates against Leishmania amazonensis infection. Parasitology 146:3322–32
     [Google Scholar]
  96. 96. 
    Tao P, Mahalingam M, Kirtley ML, van Lier CJ, Sha J et al. 2013. Mutated and bacteriophage T4 nanoparticle arrayed F1-V immunogens from Yersinia pestis as next generation plague vaccines. PLOS Pathog 9:7e1003495
     [Google Scholar]
  97. 97. 
    Iwagami Y, Casulli S, Nagaoka K, Kim M, Carlson RI et al. 2017. Lambda phage-based vaccine induces antitumor immunity in hepatocellular carcinoma. Heliyon 3:900407
     [Google Scholar]
  98. 98. 
    Villa-Mancera A, Quiroz-Romero H, Correa D, Ibarra F, Reyes-Pérez M et al. 2008. Induction of immunity in sheep to Fasciola hepatica with mimotopes of cathepsin L selected from a phage display library. Parasitology 135:121437–45
     [Google Scholar]
  99. 99. 
    Eriksson F, Tsagozis P, Lundberg K, Parsa R, Mangsbo SM et al. 2009. Tumor-specific bacteriophages induce tumor destruction through activation of tumor-associated macrophages. J. Immunol. 182:53105–11Phage treatment switches an M2 polarizing tumor microenvironment to M1 polarizing in a TLR-dependent manner and is associated with tumor regression.
     [Google Scholar]
  100. 100. 
    Kumar AB, Mishrad AAK, Prakash C, Priyadarshini A, Rawat M 2018. Immunization with Salmonella Abortusequi phage lysate protects guinea pig against the virulent challenge of SAE-742. Biologicals 56:24–28
     [Google Scholar]
  101. 101. 
    Bodner K, Melkonian AL, Barth AIM, Kudo T, Tanouchi Y, Covert MW. 2020. Engineered fluorescent E. coli lysogens allow live-cell imaging of functional prophage induction triggered inside macrophages. Cell Syst 10:3254–64
     [Google Scholar]
  102. 102. 
    Tiwari BR, Kim S, Rahman M, Kim J. 2011. Antibacterial efficacy of lytic Pseudomonas bacteriophage in normal and neutropenic mice models. J. Microbiol. 49:6994–99
     [Google Scholar]
  103. 103. 
    Roach DR, Leung CY, Henry M, Morello E, Singh D et al. 2017. Synergy between the host immune system and bacteriophage is essential for successful phage therapy against an acute respiratory pathogen. Cell Host Microbe 22:138–47.e4Phages work synergistically with neutrophils to protect in a murine model of Pseudomonas aeruginosa pneumonia.
     [Google Scholar]
  104. 104. 
    Borysowski J, Międzybrodzki R, Wierzbicki P, Kłosowska D, Korczak-Kowalska G et al. 2017. A3R phage and Staphylococcus aureus lysate do not induce neutrophil degranulation. Viruses 9:236
     [Google Scholar]
  105. 105. 
    Freyberger HR, He Y, Roth AJ, Nikolich MP, Filippov AA. 2018. Effects of Staphylococcus aureus bacteriophage K on expression of cytokines and activation markers by human dendritic cells in vitro. Viruses 10:11617
     [Google Scholar]
  106. 106. 
    Hong Y, Thimmapuram J, Zhang J, Collings CK, Bhide K et al. 2016. The impact of orally administered phages on host immune response and surrounding microbial communities. Bacteriophage 6:3e1211066
     [Google Scholar]
  107. 107. 
    Jończyk-Matysiak E, Łusiak-Szelachowska M, Kłak M, Bubak B, Międzybrodzki R et al. 2015. The effect of bacteriophage preparations on intracellular killing of bacteria by phagocytes. J. Immunol. Res. 2015:482863
     [Google Scholar]
  108. 108. 
    Bocian K, Borysowski J, Zarzycki M, Wierzbicki P, Klosowska D et al. 2016. LPS-activated monocytes are unresponsive to T4 phage and T4-generated Escherichia coli lysate. Front. Microbiol. 7:1356
     [Google Scholar]
  109. 109. 
    Miernikiewicz P, Dąbrowska K, Piotrowicz A, Owczarek B, Wojas-Turek J et al. 2013. T4 phage and its head surface proteins do not stimulate inflammatory mediator production. PLOS ONE 8:8e71036
     [Google Scholar]
  110. 110. 
    Borysowski J, Wierzbicki P, Kłosowska D, Korczak-Kowalska G, Weber-Dąbrowska B, Andrzej G 2010. The effects of T4 and A3/R phage preparations on whole-blood monocyte and neutrophil respiratory burst. Viral Immunol. 23:5541–44
     [Google Scholar]
  111. 111. 
    Zhvania P, Hoyle NS, Nadareishvili L, Nizharadze D, Kutateladze M. 2017. Phage therapy in a 16-year-old boy with Netherton syndrome. Front. Med. 4:94
     [Google Scholar]
  112. 112. 
    Rice SA, Tan CH, Mikkelsen PJ, Kung V, Woo J et al. 2009. The biofilm life cycle and virulence of Pseudomonas aeruginosa are dependent on a filamentous prophage. ISME J 3:3271–82
     [Google Scholar]
  113. 113. 
    Burgener EB, Sweere JM, Bach MS, Secor PR, Haddock N et al. 2019. Filamentous bacteriophages are associated with chronic Pseudomonas lung infections and antibiotic resistance in cystic fibrosis. Sci. Transl. Med. 11:488eaau9748
     [Google Scholar]
  114. 114. 
    Przerwa A, Zimecki M, Świtała-Jeleń K, Da̧browska K, Krawczyk E et al. 2006. Effects of bacteriophages on free radical production and phagocytic functions. Med. Microbiol. Immunol. 195:3143–50
     [Google Scholar]
  115. 115. 
    Miedzybrodzki R, Switala-Jelen K, Fortuna W, Weber-Dabrowska B, Przerwa A et al. 2008. Bacteriophage preparation inhibition of reactive oxygen species generation by endotoxin-stimulated polymorphonuclear leukocytes. Virus Res 131:2233–42
     [Google Scholar]
  116. 116. 
    Jahn MT, Arkhipova K, Markert SM, Stigloher C, Lachnit T et al. 2019. A phage protein aids bacterial symbionts in eukaryote immune evasion. Cell Host Microbe 26:4542–50.e5
     [Google Scholar]
  117. 117. 
    Van Belleghem JD, Clement F, Merabishvili M, Lavigne R, Vaneechoutte M et al. 2017. Pro- and anti-inflammatory responses of peripheral blood mononuclear cells induced by Staphylococcus aureus and Pseudomonas aeruginosa phages. Sci. Rep 7:18004Phages from Staphylococcus aureus and Pseudomonas aeruginosa direct cytokine expression of human peripheral monocytes that is independent of endotoxin.
     [Google Scholar]
  118. 118. 
    Tao P, Zhu J, Mahalingam M, Batra H, Rao VB. 2019. Bacteriophage T4 nanoparticles for vaccine delivery against infectious diseases. Adv. Drug Deliv. Rev. 145:57–72
     [Google Scholar]
  119. 119. 
    Dufour N, Henry M, Ricard J-D, Debarbieux L, Khan Mirzaei M et al. 2016. Commentary: morphologically distinct Escherichia coli bacteriophages differ in their efficacy and ability to stimulate cytokine release in vitro. Front. Microbiol. 7:1029
     [Google Scholar]
  120. 120. 
    Sapinoro R, Volcy K, Rodrigo WWSI, Schlesinger JJ, Dewhurst S. 2008. Fc receptor-mediated, antibody-dependent enhancement of bacteriophage lambda-mediated gene transfer in mammalian cells. Virology 373:2274–86
     [Google Scholar]
  121. 121. 
    Delmastro P, Meola A, Monaci P, Cortese R, Galfrè G 1997. Immunogenicity of filamentous phage displaying peptide mimotopes after oral administration. Vaccine 15:111276–85
     [Google Scholar]
  122. 122. 
    Majewska J, Beta W, Lecion D, Hodyra-Stefaniak K, Kłopot A et al. 2015. Oral application of T4 phage induces weak antibody production in the gut and in the blood. Viruses 7:84783–99
     [Google Scholar]
  123. 123. 
    Dąbrowska K, Miernikiewicz P, Piotrowicz A, Hodyra K, Owczarek B et al. 2014. Immunogenicity studies of proteins forming the T4 phage head surface. J. Virol. 88:2112551–57
     [Google Scholar]
  124. 124. 
    Biswas B, Adhya S, Washart P, Paul B, Trostel AN et al. 2002. Bacteriophage therapy rescues mice bacteremic from a clinical isolate of vancomycin-resistant Enterococcus faecium. Infect. Immun. 70:1204–10
     [Google Scholar]
  125. 125. 
    Inchley CJ, Howard JG. 1969. The immunogenicity of phagocytosed T4 bacteriophage: cell replacement studies with splenectomized and irradiated mice. Clin. Exp. Immunol. 5:1189–98
     [Google Scholar]
  126. 126. 
    Sullivan JL, Schiffman G, Miser J, Ochs HD, Hammerschlag MR et al. 1978. Immune response after splenectomy. Lancet 311:8057178–81
     [Google Scholar]
  127. 127. 
    Gaubin M, Fanutti C, Mishal Z, Durrbach A, De Berardinis P et al. 2003. Processing of filamentous bacteriophage virions in antigen-presenting cells targets both HLA class I and class II peptide loading compartments. DNA Cell Biol 22:111–18
     [Google Scholar]
  128. 128. 
    Wan Y, Wu Y, Zhou J, Zou L, Liang Y et al. 2005. Cross-presentation of phage particle antigen in MHC class II and endoplasmic reticulum marker-positive compartments. Eur. J. Immunol. 35:72041–50
     [Google Scholar]
  129. 129. 
    Lotfi Z, Golchin M, Khalili-Yazdi A, Khalili M. 2019. Immunological properties of the SLLTEVET epitope of Influenza A virus in multiple display on filamentous M13 phage. Comp. Immunol. Microbiol. Infect. Dis. 65:76–80
     [Google Scholar]
  130. 130. 
    Majewska J, Kaźmierczak Z, Lahutta K, Lecion D, Szymczak A et al. 2019. Induction of phage-specific antibodies by two therapeutic staphylococcal bacteriophages administered per os. Front. Immunol. 14:102607
     [Google Scholar]
  131. 131. 
    Łusiak-Szelachowska M, Zaczek M, Weber-Dabrowska B, Miȩdzybrodzki R, Kłak M et al. 2014. Phage neutralization by sera of patients receiving phage therapy. Viral Immunol 27:6295–304
     [Google Scholar]
  132. 132. 
    Smith LL, Buckley R, Lugar P. 2014. Diagnostic immunization with bacteriophage ΦX 174 in patients with common variable immunodeficiency/hypogammaglobulinemia. Front. Immunol. 5:410
     [Google Scholar]
  133. 133. 
    Bearden CM, Agarwal A, Book BK, Vieira CA, Sidner RA et al. 2005. Rituximab inhibits the in vivo primary and secondary antibody response to a neoantigen, bacteriophage phiX174. Am. J. Transplant. 5:150–57
     [Google Scholar]
  134. 134. 
    Kucharewicz-Krukowska A, Slopek S. 1987. Immunogenic effect of bacteriophage in patients subjected to phage therapy. Arch. Immunol. Ther. Exp. 35:5553–61
     [Google Scholar]
  135. 135. 
    Krag DN, Shukla GS, Shen GP, Pero S, Ashikaga T et al. 2006. Selection of tumor-binding ligands in cancer patients with phage display libraries. Cancer Res 66:157724–33
     [Google Scholar]
  136. 136. 
    Dabrowska K, Zembala M, Boratynski J, Switala-Jelen K, Wietrzyk J et al. 2007. Hoc protein regulates the biological effects of T4 phage in mammals. Arch. Microbiol. 187:6489–98
     [Google Scholar]
  137. 137. 
    Dabrowska K, Opolski A, Wietrzyk J, Switala-Jelen K, Godlewska J et al. 2004. Anticancer activity of bacteriophage T4 and its mutant HAP1 in mouse experimental tumour models. Anticancer Res 24:63991–95
     [Google Scholar]
  138. 138. 
    Hodyra-Stefaniak K, Lahutta K, Majewska J, Kaźmierczak Z, Lecion D et al. 2019. Bacteriophages engineered to display foreign peptides may become short-circulating phages. Microb. Biotechnol. 12:4730–41
     [Google Scholar]
  139. 139. 
    Sokoloff AV, Bock I, Zhang G, Sebestyén MG, Wolff JA. 2000. The interactions of peptides with the innate immune system studied with use of T7 phage peptide display. Mol. Ther. 2:2131–39
     [Google Scholar]
  140. 140. 
    Wan Y, Wu Y, Bian J, Wang XZ, Zhou W et al. 2001. Induction of hepatitis B virus-specific cytotoxic T lymphocytes response in vivo by filamentous phage display vaccine. Vaccine 19:20–222918–23
     [Google Scholar]
  141. 141. 
    Sartorius R, Pisu P, D'Apice L, Pizzella L, Romano C et al. 2008. The use of filamentous bacteriophage fd to deliver MAGE-A10 or MAGE-A3 HLA-A2-restricted peptides and to induce strong antitumor CTL responses. J. Immunol. 180:63719–28
     [Google Scholar]
  142. 142. 
    Cuesta AM, Suárez E, Larsen M, Jensen KB, Sanz L et al. 2006. Enhancement of DNA vaccine potency through linkage of antigen to filamentous bacteriophage coat protein III domain I. Immunology 117:4502–6
     [Google Scholar]
  143. 143. 
    Zimecki M, Weber-Dabrowska B, Łusiak-Szelachowska M, Mulczyk M, Boratyński J et al. 2003. Bacteriophages provide regulatory signals in mitogen-induced murine splenocyte proliferation. Cell. Mol. Biol. Lett. 8:3699–711
     [Google Scholar]
  144. 144. 
    Ulivieri C, Citro A, Ivaldi F, Mascolo D, Ghittoni R et al. 2008. Antigenic properties of HCMV peptides displayed by filamentous bacteriophages versus synthetic peptides. Immunol. Lett. 119:62–70
     [Google Scholar]
  145. 145. 
    Fogelman I, Davey V, Ochs HD, Elashoff M, Feinberg MB et al. 2000. Evaluation of CD4+ T cell function in vivo in HIV-infected patients as measured by bacteriophage phiX174 immunization. J. Infect. Dis. 182:2435–41
     [Google Scholar]
  146. 146. 
    Fluckiger A, Daillère R, Sassi M, Sixt BS, Liu P et al. 2020. Cross-reactivity between tumor MHC class I-restricted antigens and an enterococcal bacteriophage. Science 369:6506936–42Prophage gene expression in tumor-associated Enterococcus directs T cell immunity and promotes tumor clearance and survival to PD-1 immunotherapy.
     [Google Scholar]
/content/journals/10.1146/annurev-virology-091919-074551
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Bacteriophages and the Immune System
Annual Review of Virology 8, 415 (2021); https://doi.org/10.1146/annurev-virology-091919-074551
/content/journals/10.1146/annurev-virology-091919-074551
/content/journals/10.1146/annurev-virology-091919-074551
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