Persistent Infections and Immunity in Ruminants to Arthropod-Borne Bacteria in the Family Anaplasmataceae

Literature Cited

1. Dumler JS, Choi KS, Garcia-Garcia JC, Barat NS, Scorpio DG. 1.  et al. 2005. Human granulocytic anaplasmosis and Anaplasma phagocytophilum. Emerg. Infect. Dis. 11:1828–34 [Google Scholar]
2. Dumler JS. 2.  2012. The biological basis of severe outcomes in Anaplasma phagocytophilum infection. FEMS Immunol. Med. Microbiol. 64:13–20 [Google Scholar]
3. Dumler JS, Barbet AF, Bekker CP, Dasch GA, Palmer GH. 3.  et al. 2001. Reorganization of genera in the families Rickettsiaceae and Anaplasmataceae in the order Rickettsiales: unification of some species of Ehrlichia with Anaplasma, Cowdria with Ehrlichia and Ehrlichia with Neorickettsia, descriptions of six new species combinations and designation of Ehrlichia equi and ‘HGE agent’ as subjective synonyms of Ehrlichia phagocytophila. Int. J. Syst. Evol. Microbiol. 51:2145–65 [Google Scholar]
4. Rikihisa Y. 4.  2003. Mechanisms to create a safe haven by members of the family Anaplasmataceae. Ann. N.Y. Acad. Sci. 990:548–55 [Google Scholar]
5. Rikihisa Y. 5.  2011. Mechanisms of obligatory intracellular infection with Anaplasma phagocytophilum. Clin. Microbiol. Rev. 24:469–89 [Google Scholar]
6. Allred DR. 6.  1998. Antigenic variation in Babesia bovis: How similar is it to that in Plasmodium falciparum?. Ann. Trop. Med. Parasitol. 92:461–72 [Google Scholar]
7. Young D, Hussell T, Dougan G. 7.  2002. Chronic bacterial infections: living with unwanted guests. Nat. Immunol. 3:1026–32 [Google Scholar]
8. Barbour AG, Restrepo BI. 8.  2000. Antigenic variation in vector-borne pathogens. Emerg. Infect. Dis. 6:449–57 [Google Scholar]
9. Ficht TA. 9.  2003. Intracellular survival of Brucella: defining the link with persistence. Vet. Microbiol. 92:213–23 [Google Scholar]
10. Palmer GH, Brayton KA. 10.  2013. Antigenic variation and transmission fitness as drivers of bacterial strain structure. Cell. Microbiol. 15:1969–75 [Google Scholar]
11. Andrew HR, Norval RA. 11.  1989. The carrier status of sheep, cattle and African buffalo recovered from heartwater. Vet. Parasitol. 34:261–66 [Google Scholar]
12. French DM, McElwain TF, McGuire TC, Palmer GH. 12.  1998. Expression of Anaplasma marginale major surface protein 2 variants during persistent cyclic rickettsemia. Infect. Immun. 66:1200–7 [Google Scholar]
13. French DM, Brown WC, Palmer GH. 13.  1999. Emergence of Anaplasma marginale antigenic variants during persistent rickettsemia. Infect. Immun. 67:5834–40 [Google Scholar]
14. Scoles GA, Broce AB, Lysyk TJ, Palmer GH. 14.  2005. Relative efficiency of biological transmission of Anaplasma marginale (Rickettsiales: Anaplasmataceae) by Dermacentor andersoni (Acari: Ixodidae) compared with mechanical transmission by Stomoxys calcitrans (Diptera: Musciidae). J. Med. Entomol. 42:66–75 [Google Scholar]
15. Scoles GA, Miller JA, Foil LD. 15.  2008. Comparison of the efficiency of biological transmission of Anaplasma marginale (Rickettsiales: Anaplasmataceae) by Dermacentor andersoni Stiles (Acari: Ixodidae) with mechanical transmission by the horse fly, Tabanus fuscicostatus Hine (Diptera: Muscidae). J. Med. Entomol. 45:109–14 [Google Scholar]
16. Meeus PF, Brayton KA, Palmer GH, Barbet AF. 16.  2003. Conservation of a gene conversion mechanism in two distantly related paralogues of Anaplasma marginale. Mol. Microbiol. 47:633–43 [Google Scholar]
17. Brayton KA, Meeus PF, Barbet AF, Palmer GH. 17.  2003. Simultaneous variation of the immunodominant outer membrane proteins, MSP2 and MSP3, during Anaplasma marginale persistence in vivo. Infect. Immun. 71:6627–32 [Google Scholar]
18. Palmer GH, Abbott JR, French DM, McElwain TF. 18.  1998. Persistence of Anaplasma ovis infection and conservation of the msp-2 and msp-3 multigene families within the genus Anaplasma. Infect. Immun. 66:6035–39 [Google Scholar]
19. Stuen S, Casey ANJ, Woldehiwet Z, French NP, Ogden NH. 19.  2006. Detection by the polymerase chain reaction of Anaplasma phagocytophilum in tissues of persistently infected sheep. J. Comp. Pathol. 134:101–4 [Google Scholar]
20. Stuen S, Bråten M, Bergström K, Bårdsen K. 20.  2008. Cyclic variation in lambs infected with Anaplasma phagocytophilum. Vet. Rec. 163:338–40 [Google Scholar]
21. Thomas RJ, Birtles RJ, Radford AD, Woldehiwet Z. 21.  2012. Recurrent bacteraemia in sheep infected persistently with Anaplasma phagocytophilum. J. Comp. Pathol. 147:360–67 [Google Scholar]
22. Ogden NH, Casey ANJ, Woldehiwet Z, French NP. 22.  2003. Transmission of Anaplasma phagocytophilum to Ixodes ricinus ticks from sheep in the acute and post-acute phases of infection. Infect. Immun. 71:2071–78 [Google Scholar]
23. Granquist EG, Stuen S, Lundgren AM, Bråten M, Barbet AF. 23.  2008. Outer membrane protein sequence variation in lambs experimentally infected with Anaplasma phagocytophilum. Infect. Immun. 76:120–26 [Google Scholar]
24. Granquist EG, Stuen S, Crosby FL, Lundgren AM, Alleman AR, Barbet AF. 24.  2010. Variant-specific and diminishing immune responses towards the highly variable MSP2(P44) outer membrane protein of Anaplasma phagocytophilum during persistent infection in lambs. Vet. Immunol. Immunopathol. 133:117–24 [Google Scholar]
25. Thomas RJ, Radford AD, Birtles RJ, Woldehiwet Z. 25.  2013. Expression of p44 variant-specific antibodies in sheep persistently infected with Anaplasma phagocytophilum. Vet. Microbiol. 167:484–93 [Google Scholar]
26. Brayton KA, Kappmeyer LS, Herndon DR, Dark MJ, Tibbals DL. 26.  et al. 2005. Complete genome sequencing of Anaplasma marginale reveals that the surface is skewed to two superfamilies of outer membrane proteins. PNAS 102:844–49 [Google Scholar]
27. Barbet AF, Lundgren A, Yi J, Rurangirwa FR, Palmer GH. 27.  2000. Antigenic variation of Anaplasma marginale by expression of MSP2 mosaics. Infect. Immun. 68:6133–38 [Google Scholar]
28. Brayton KA, Palmer GH, Lundgren A, Yi J, Barbet AF. 28.  2002. Antigenic variation of Anaplasma marginale msp2 occurs by combinatorial gene conversion. Mol. Microbiol. 43:1151–59 [Google Scholar]
29. Brayton KA, Knowles DP, McGuire TC, Palmer GH. 29.  2001. Efficient use of a small genome to generate antigenic diversity in tick-borne ehrlichial pathogens. PNAS 98:4130–35 [Google Scholar]
30. Futse JE, Brayton KA, Knowles DP Jr, Palmer GH. 30.  2005. Structural basis for segmental gene conversion in generation of Anaplasma marginale outer membrane protein variants. Mol. Microbiol. 57:212–21 [Google Scholar]
31. Palmer GH, Bankhead T, Lukehart SA. 31.  2009. ‘Nothing is permanent but change’—antigenic variation in persistent bacterial pathogens. Cell. Microbiol. 11:1697–705 [Google Scholar]
32. Dark MJ, Herndon DR, Kappmeyer LS, Gonzales MP, Nordeen E. 32.  et al. 2009. Conservation in the face of diversity: multistrain analysis of an intracellular bacterium. BMC Genomics 10:16 [Google Scholar]
33. Dark MJ, Lundgren AM, Barbet AF. 33.  2012. Determining the repertoire of immunodominant proteins via whole-genome amplification of intracellular pathogens. PLOS ONE 7:e36456 [Google Scholar]
34. Rodriguez JL, Palmer GH, Knowles DP Jr, Brayton KA. 34.  2005. Distinctly different msp2 pseudogene repertoires in Anaplasma marginale strains that are capable of superinfection. Gene 361:127–32 [Google Scholar]
35. Futse JE, Brayton KA, Dark MJ, Knowles DP Jr, Palmer GH. 35.  2008. Superinfection as a driver of genomic diversification in antigenically variant pathogens. PNAS 105:2123–27 [Google Scholar]
36. Palmer GH, Futse JE, Leverich CK, Knowles DP Jr, Rurangirwa FR, Brayton KA. 36.  2007. Selection for simple major surface protein 2 variants during Anaplasma marginale transmission to immunologically naive animals. Infect. Immun. 75:1502–6 [Google Scholar]
37. Futse JE, Brayton KA, Nydam SD, Palmer GH. 37.  2009. Generation of antigenic variants via gene conversion: evidence for recombination fitness selection at the locus level in Anaplasma marginale. Infect. Immun. 77:3181–87 [Google Scholar]
38. Kocan KM, de la Fuente J, Blouin EF, Coetzee JF, Ewing SA. 38.  2010. The natural history of Anaplasma marginale. Vet. Parasitol. 167:95–107 [Google Scholar]
39. Turse JE, Scoles GA, Deringer JR, Fry LM, Brown WC. 39.  2014. Immunization-induced Anaplasma marginale-specific T-lymphocyte responses impaired by A. marginale infection are restored after eliminating infection with tetracycline. Clin. Vaccine Immunol. 21:1369–75 [Google Scholar]
40. Han S, Norimine J, Brayton KA, Palmer GH, Scoles GA, Brown WC. 40.  2010. Anaplasma marginale infection with persistent high-load bacteremia induces a dysfunctional memory CD4⁺ T lymphocyte response but sustained high IgG titers. Clin. Vaccine Immunol. 17:1881–90 [Google Scholar]
41. Visser ES, McGuire TC, Palmer GH, Davis WC, Shkap V. 41.  et al. 1992. The Anaplasma marginale msp5 gene encodes a 19-kilodalton protein conserved in all recognized Anaplasma species. Infect. Immun. 60:5139–44 [Google Scholar]
42. Gale KR, Leatch G, Gartside M, Dimmock CM. 42.  1992. Anaplasma marginale: failure of sera from immune cattle to confer protection in passive-transfer experiments. Parasitol. Res. 78:410–15 [Google Scholar]
43. Palmer GH, Rurangirwa FR, Kocan KM, Brown WC. 43.  1999. Molecular basis for vaccine development against the ehrlichial pathogen Anaplasma marginale. Parasitol. Today 15:281–86 [Google Scholar]
44. Brown WC, Shkap V, Zhu D, McGuire TC, Tuo W. 44.  et al. 1998. CD4⁺ T-lymphocyte and immunoglobulin G2 responses in calves immunized with Anaplasma marginale outer membranes and protected against homologous challenge. Infect. Immun. 66:5406–13 [Google Scholar]
45. Noh SM, Brayton KA, Brown WC, Norimine J, Munske GR. 45.  et al. 2008. Composition of the surface proteome of Anaplasma marginale and its role in protective immunity induced by outer membrane immunization. Infect. Immun. 76:2219–26 [Google Scholar]
46. Palmer GH, Munodzana D, Tebele N, Ushe T, McElwain TF. 46.  1994. Heterologous strain challenge of cattle immunized with Anaplasma marginale outer membranes. Vet. Immunol. Immunopathol. 42:265–73 [Google Scholar]
47. Tebele N, McGuire TC, Palmer GH. 47.  1991. Induction of protective immunity by using Anaplasma marginale initial body membranes. Infect. Immun. 59:3199–204 [Google Scholar]
48. Tebele N, Palmer GH. 48.  1991. Crossprotective immunity between the Florida and a Zimbabwe stock of Anaplasma marginale. Trop. Anim. Health Prod. 23:197–202 [Google Scholar]
49. Noh SM, Zhuang Y, Futse JE, Brown WC, Brayton KA, Palmer GH. 49.  2010. The immunization-induced antibody response to the Anaplasma marginale major surface protein 2 and its association with protective immunity. Vaccine 28:3741–47 [Google Scholar]
50. Noh SM, Brown WC. 50.  2012. Adaptive immune responses to infection and opportunities for vaccine development. Intracellular Pathogens II: Rickettsiales GH Palmer, AF Azad 328–63 Washington, DC: ASM Press [Google Scholar]
51. Palmer GH, Brown WC, Noh SM, Brayton KA. 51.  2012. Genome-wide screening and identification of antigens for rickettsial vaccine development. FEMS Immunol. Med. Microbiol. 64:115–19 [Google Scholar]
52. Lopez JE, Siems WF, Palmer GH, Brayton KA, McGuire TC. 52.  et al. 2005. Identification of novel antigenic proteins in a complex Anaplasma marginale outer membrane immunogen by mass spectrometry and genomic mapping. Infect. Immun. 73:8109–18 [Google Scholar]
53. Lopez JE, Palmer GH, Brayton KA, Dark MJ, Leach SE, Brown WC. 53.  2007. Immunogenicity of Anaplasma marginale type IV secretion system proteins in a protective outer membrane vaccine. Infect. Immun. 75:2333–42 [Google Scholar]
54. Abbott JR, Palmer GH, Howard CJ, Hope JC, Brown WC. 54.  2004. Anaplasma marginale major surface protein 2 CD4⁺-T-cell epitopes are evenly distributed in conserved and hypervariable regions (HVR), whereas linear B-cell epitopes are predominantly located in the HVR. Infect. Immun. 72:7360–66 [Google Scholar]
55. Brown WC, McGuire TC, Zhu D, Lewin HA, Sosnow J, Palmer GH. 55.  2001. Highly conserved regions of the immunodominant major surface protein 2 of the genogroup II ehrlichial pathogen Anaplasma marginale are rich in naturally derived CD4⁺ T lymphocyte epitopes that elicit strong recall responses. J. Immunol. 166:1114–24 [Google Scholar]
56. Brown WC, Brayton KA, Styer CM, Palmer GH. 56.  2003. The hypervariable region of Anaplasma marginale major surface protein 2 (MSP2) contains multiple immunodominant CD4⁺ T lymphocyte epitopes that elicit variant-specific proliferative and IFN-γ responses in MSP2 vaccinates. J. Immunol. 170:3790–98 [Google Scholar]
57. Brown WC. 57.  2008. Unraveling the immune regulatory mechanisms imposed by Anaplasma. Vet. J. 175:10–11 [Google Scholar]
58. Brown WC. 58.  2012. Adaptive immunity to Anaplasma pathogens and immune dysregulation: implications for bacterial persistence. Comp. Immunol. Microbiol. Infect. Dis. 35:241–52 [Google Scholar]
59. Dunning Hotopp JC, Lin M, Madupu R, Crabtree J, Angiuoli SV. 59.  et al. 2006. Comparative genomics of emerging human ehrlichiosis agents. PLOS Genet. 2:e21 [Google Scholar]
60. Sorbara MT, Philpott DJ. 60.  2011. Peptidoglycan: a critical activator of the mammalian immune system during infection and homeostasis. Immunol. Rev. 243:40–60 [Google Scholar]
61. Ulevitch RJ, Mathison JC, da Silva CJ. 61.  2004. Innate immune responses during infection. Vaccine 22:Suppl. 1S25–S30 [Google Scholar]
62. Abbott JR, Palmer GH, Kegerreis KA, Hetrick PF, Howard CJ. 62.  et al. 2005. Rapid and long-term disappearance of CD4⁺ T lymphocyte responses specific for Anaplasma marginale major surface protein-2 (MSP2) in MSP2 vaccinates following challenge with live A. marginale. J. Immunol. 174:6702–15 [Google Scholar]
63. Brown WC, Turse JE, Lawrence PK, Johnson WC, Scoles GA. 63.  et al. 2015. Loss of immunization-induced epitope-specific CD4⁺ T cell response following Anaplasma marginale infection requires the presence of the T-cell epitope on the pathogen but is not associated with an increase in lymphocytes expressing known regulatory cell phenotypes. Clin. Vaccine Immunol. 22:742–53 [Google Scholar]
64. Han S, Norimine J, Palmer GH, Mwangi W, Lahmers KK, Brown WC. 64.  2008. Rapid deletion of antigen-specific CD4⁺ T cells following infection represents a strategy of immune evasion and persistence for Anaplasma marginale. J. Immunol. 181:7759–69 [Google Scholar]
65. Mebius RE, Kraal G. 65.  2005. Structure and function of the spleen. Nat. Rev. Immunol. 5:606–16 [Google Scholar]
66. Norimine J, Han S, Brown WC. 66.  2006. Quantitation of Anaplasma marginale major surface protein (MSP)1a and MSP2 epitope-specific CD4⁺ T lymphocytes using bovine DRB3*1101 and DRB3*1201 tetramers. Immunogenetics 58:726–39 [Google Scholar]
67. Moskophidis D, Lechner F, Pircher H, Zingernagel RM. 67.  1993. Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector cells. Nature 362:758–61 [Google Scholar]
68. Klenerman P, Hill A. 68.  2005. T cells and viral persistence: lessons from diverse infections. Nat. Immunol. 6:873–79 [Google Scholar]
69. Freeman GJ, Wherry EJ, Ahmed R, Sharpe AH. 69.  2006. Reinvigorating exhausted HIV-specific T cells via PD-1–PD-1 ligand blockade. J. Exp. Med. 203:2223–27 [Google Scholar]
70. Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP. 70.  et al. 2006. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439:682–87 [Google Scholar]
71. Sharpe AH, Wherry EJ, Ahmed R, Freeman GJ. 71.  2007. The function of programmed cell death and its ligands in regulating autoimmunity and infection. Nat. Immunol. 8:239–45 [Google Scholar]
72. Mueller SN, Ahmed R. 72.  2009. High antigen levels are the cause of T cell exhaustion during chronic viral infection. PNAS 106:8623–28 [Google Scholar]
73. Blackburn SD, Crawford A, Shin H, Polley A, Freeman GJ, Wherry EJ. 73.  2010. Tissue-specific differences in PD-1 and PD-L1 expression during chronic viral infection: implications for CD8 T-cell exhaustion. J. Virol. 84:2078–89 [Google Scholar]
74. Wherry EJ. 74.  2011. T cell exhaustion. Nat. Immunol. 12:492–99 [Google Scholar]
75. Klenerman P, Thimme R. 75.  2012. T cell responses in hepatitis C: the good, the bad, the unconventional. Gut 61:1226–34 [Google Scholar]
76. Duraiswamy J, Freeman GJ, Coukos G. 76.  2013. Therapeutic PD-1 pathway blockade augments with other modalities of immunotherapy T-cell function to prevent immune decline in ovarian cancer. Cancer Res. 73:6900–12 [Google Scholar]
77. West EE, Jin H-T, Rasheed A-U, Penaloza-MacMaster P, Ha S-J. 77.  et al. 2013. PD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells. J. Clin. Investig. 123:2604–15 [Google Scholar]
78. Butler NS, Moebius J, Pewe LL, Traore B, Doumbo OK. 78.  et al. 2012. Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection. Nat. Immunol. 13:188–95 [Google Scholar]
79. Crawford A, Angelosanto JM, Kao C, Doering TA, Odorizzi PM. 79.  et al. 2014. Molecular and transcriptional basis of CD4⁺ T cell dysfunction during chronic infection. Immunity 40:289–302 [Google Scholar]
80. Illingworth J, Butler NS, Roetynck S, Mwacharo J, Pierce SK. 80.  et al. 2013. Chronic exposure to Plasmodium falciparum is associated with phenotypic evidence of B and T cell exhaustion. J. Immunol. 190:1038–47 [Google Scholar]
81. Han S, Asoyan A, Rabenstein H, Nakano N, Obst R. 81.  2010. Role of antigen persistence and dose for CD4⁺ T-cell exhaustion and recovery. PNAS 107:20453–58 [Google Scholar]
82. Eriks IS, Palmer GH, McGuire TC, Allred DR, Barbet AF. 82.  1989. Detection and quantitation of Anaplasma marginale in carrier cattle by using a nucleic acid probe. J. Clin. Microbiol. 27:279–84 [Google Scholar]
83. Reinbold JB, Coetzee JF, Hollis LC, Nickell JS, Riegel C. 83.  et al. 2010. The efficacy of three chlortetracycline regimens in the treatment of persistent Anaplasma marginale infection. Vet. Microbiol. 145:69–75 [Google Scholar]
84. Guzman E, Price S, Poulsom H, Hope J. 84.  2012. Bovine γδ T cells: cells with multiple functions and important roles in immunity. Vet. Immunol. Immunopathol. 148:161–67 [Google Scholar]
85. Guzman E, Hope J, Taylor G, Smith AL, Cubillos-Zapata C, Charleston B. 85.  2014. Bovine γδ T cells are a major regulatory T cell subset. J. Immunol. 193:208–22 [Google Scholar]
86. Hoek A, Rutten VP, Kool J, Arkesteijn GJ, Bouwstra RJ. 86.  et al. 2009. Subpopulations of bovine WC1⁺ γδ T cells rather than CD4⁺CD25^high Foxp3⁺ T cells act as immune regulatory cells ex vivo. Vet. Res. 40:6 [Google Scholar]
87. McGill JL, Nonnecke BJ, Lippolis JD, Reinhardt TA, Sacco RE. 87.  2013. Differential chemokine and cytokine production by neonatal bovine γδ T-cell subsets in response to viral toll-like receptor agonists and in vivo respiratory syncytial virus infection. Immunology 139:227–44 [Google Scholar]
88. Ikebuchi R, Konnai S, Sunden Y, Onuma M, Ohashi K. 88.  2010. Molecular cloning and expression analysis of bovine programmed death-1. Microbiol. Immunol. 54:291–98 [Google Scholar]
89. Ikebuchi R, Konnai S, Shirai T, Sunden Y, Murata S. 89.  et al. 2011. Increase of cells expressing PD-L1 in bovine leukemia virus infection and enhancement of anti-viral immune responses in vitro via PD-L1 blockade. Vet. Res. 42:103 [Google Scholar]
90. Ikebuchi R, Konnai S, Okagawa T, Yokoyama K, Nakajima C. 90.  et al. 2013. Blockade of bovine PD-1 increases T cell function and inhibits bovine leukemia virus expression in B cells in vitro. Vet. Res. 44:59 [Google Scholar]
91. Ikebuchi R, Konnai S, Okagawa T, Yokoyama K, Nakajima C. 91.  et al. 2014. Influence of PD-L1 cross-linking on cell death in PD-L1-expressing cell lines and bovine lymphocytes. Immunology 142:551–61 [Google Scholar]
92. Konnai S, Suzuki S, Shirai T, Ikebuchi R, Okagawa T. 92.  et al. 2013. Enhanced expression of LAG-3 on lymphocyte subpopulations from persistently lymphocytotic cattle infected with bovine leukemia virus. Comp. Immunol. Microbiol. Infect. Dis. 36:63–69 [Google Scholar]
93. Barbet AF, Meeus PF, Belanger M, Bowie MV, Yi J. 93.  et al. 2003. Expression of multiple outer membrane protein sequence variants from a single genomic locus of Anaplasma phagocytophilum. Infect. Immun. 71:1706–18 [Google Scholar]
94. Barbet AF, Agnes JT, Moreland AL, Lundgren AM, Alleman AR. 94.  et al. 2005. Identification of functional promoters in the msp2 expression loci of Anaplasma marginale and Anaplasma phagocytophilum. Gene 353:89–97 [Google Scholar]
95. Lin Q, Rikihisa Y, Felek S, Wang X, Massung RF, Woldehiwet Z. 95.  2004. Anaplasma phagocytophilum has a functional msp2 gene that is distinct from p44. Infect. Immun. 72:3883–89 [Google Scholar]
96. Löhr CV, Brayton KA, Barbet AF, Palmer GH. 96.  2004. Characterization of the Anaplasma marginale msp2 locus and its synteny with the omp1/p30 loci of Ehrlichia chaffeensis and E. canis. Gene 325:115–21 [Google Scholar]
97. Lin Q, Rikihisa Y. 97.  2005. Establishment of cloned Anaplasma phagocytophilum and analysis of p44 gene conversion within an infected horse and infected SCID mice. Infect. Immun. 73:5106–14 [Google Scholar]
98. Rejmanek D, Foley P, Barbet A, Foley J. 98.  2012. Antigen variability in Anaplasma phagocytophilum during chronic infection of a reservoir host. Microbiology 158:2632–41 [Google Scholar]
99. Rejmanek D, Foley P, Barbet A, Foley J. 99.  2012. Evolution of antigen variation in the tick-borne pathogen Anaplasma phagocytophilum. Mol. Biol. Evol. 29:391–400 [Google Scholar]
100. Wang X, Cheng Z, Zhang C, Kikuchi T, Rikihisa Y. 100.  2007. Anaplasma phagocytophilum p44 mRNA expression is differentially regulated in mammalian and tick host cells: involvement of the DNA binding protein ApxR. J. Bacteriol. 189:8651–59 [Google Scholar]
101. Nelson CM, Herron MJ, Felsheim RF, Schloeder BR, Grindle SM. 101.  et al. 2008. Whole genome transcription profiling of Anaplasma phagocytophilum in human and tick host cells by tiling array analysis. BMC Genom. 9:364 [Google Scholar]
102. Lin Q, Zhang C, Rikihisa Y. 102.  2006. Analysis of involvement of the RecF pathway in p44 recombination in Anaplasma phagocytophilum and in Escherichia coli by using a plasmid carrying the p44 expression and p44 donor loci. Infect. Immun. 74:2052–62 [Google Scholar]
103. Foley JE, Nieto NC, Barbet A, Foley P. 103.  2009. Antigen diversity in the parasitic bacterium Anaplasma phagocytophilum arises from selectively-represented, spatially clustered functional pseudogenes. PLOS ONE 4:e8265 [Google Scholar]
104. Lin M, Kikuchi T, Brewer HM, Norbeck AD, Rikihisa Y. 104.  2011. Global proteomic analysis of two tick-borne emerging zoonotic agents: Anaplasma phagocytophilum and Ehrlichia chaffeensis. Front. Microbiol. 2:24 [Google Scholar]
105. Park J, Kim KJ, Grab DJ, Dumler JS. 105.  2003. Anaplasma phagocytophilum major surface protein-2 (Msp2) forms multimeric complexes in the bacterial membrane. FEMS Microbiol. Lett. 227:243–47 [Google Scholar]
106. Sarkar M, Troese MJ, Kearns SA, Yang T, Reneer DV, Carlyon JA. 106.  2008. Anaplasma phagocytophilum MSP2(P44)-18 predominates and is modified into multiple isoforms in human myeloid cells. Infect. Immun. 76:2090–98 [Google Scholar]
107. Troese MJ, Sarkar M, Galloway NL, Thomas RJ, Kearns SA. 107.  et al. 2009. Differential expression and glycosylation of Anaplasma phagocytophilum major surface protein 2 paralogs during cultivation in sialyl Lewis x-deficient host cells. Infect. Immun. 77:1746–56 [Google Scholar]
108. Alhumaidan H, Westley B, Esteva C, Berardi V, Young C, Sweeney J. 108.  2012. Transfusion-transmitted anaplasmosis from leukoreduced red blood cells. Transfusion 53:181–86 [Google Scholar]
109. Annen K, Friedman K, Eshoa C, Horowitz M, Gottschall J, Straus T. 109.  2012. Two cases of transfusion-transmitted Anaplasma phagocytophilum. Am. J. Clin. Pathol. 137:562–65 [Google Scholar]
110. Jereb M, Pecaver B, Tomazic J, Muzlovic I, Avsic-Zupanc T. 110.  et al. 2012. Severe human granulocytic anaplasmosis transmitted by blood transfusion. Emerg. Infect. Dis. 18:1354–57 [Google Scholar]
111. Leiby DA, Gill JE. 111.  2004. Transfusion-transmitted tick-borne infections: a cornucopia of threats. Transfus. Med. Rev. 18:293–306 [Google Scholar]
112. Shields K, Cumming M, Rios J, Wong MT, Zwicker JI. 112.  et al. 2014. Transfusion-associated Anaplasma phagocytophilum infection in a pregnant patient with thalassemia trait: a case report. Transfusion 55:719–25 [Google Scholar]
113. Townsend RL, Moritz ED, Fialkow LB, Berardi V, Stramer SL. 113.  2014. Probable transfusion-transmission of Anaplasma phagocytophilum by leukoreduced platelets. Transfusion 54:2828–32 [Google Scholar]
114. Woldehiwet Z. 114.  1983. Tick-borne fever: a review. Vet. Res. Commun. 6:163–75 [Google Scholar]
115. Woldehiwet Z. 115.  2006. Anaplasma phagocytophilum in ruminants in Europe. Ann. N.Y. Acad. Sci. 1078:446–60 [Google Scholar]
116. Barbet AF, Lundgren AM, Alleman AR, Stuen S, Bjöersdorff A. 116.  et al. 2006. Structure of the expression site reveals global diversity in MSP2 (P44) variants in Anaplasma phagocytophilum. Infect. Immun. 74:6429–37 [Google Scholar]
117. Casey AN, Birtles RJ, Radford AD, Bown KJ, French NP. 117.  et al. 2004. Groupings of highly similar major surface protein (p44)-encoding paralogues: a potential index of genetic diversity amongst isolates of Anaplasma phagocytophilum. Microbiology 150:727–34 [Google Scholar]
118. Dumler JS, Asanovich KM, Bakken JS. 118.  2003. Analysis of genetic identity of North American Anaplasma phagocytophilum strains by pulsed-field gel electrophoresis. J. Clin. Microbiol. 41:3392–94 [Google Scholar]
119. Barbet AF, Al-Khedery B, Stuen S, Granquist EG, Felsheim RF, Munderloh UG. 119.  2013. An emerging tick-borne disease of humans is caused by a subset of strains with conserved genome structure. Pathogens 2:544–55 [Google Scholar]
120. Al-Khedery B, Barbet AF. 120.  2014. Comparative genomics identifies a potential marker of human-virulent Anaplasma phagocytophilum. Pathogens 3:25–35 [Google Scholar]
121. Kahlon A, Ojogun N, Ragland SA, Seidman D, Troese MJ. 121.  et al. 2013. Anaplasma phagocytophilum Asp14 is an invasin that interacts with mammalian host cells via its C terminus to facilitate infection. Infect. Immun. 81:65–79 [Google Scholar]
122. Ojogun N, Kahlon A, Ragland SA, Troese MJ, Mastronunzio JE. 122.  et al. 2012. Anaplasma phagocytophilum outer membrane protein A interacts with sialylated glycoproteins to promote infection of mammalian host cells. Infect. Immun. 80:3748–60 [Google Scholar]
123. Seidman D, Ojogun N, Walker NJ, Mastronunzio J, Kahlon A. 123.  et al. 2014. Anaplasma phagocytophilum surface protein AipA mediates invasion of mammalian host cells. Cell. Microbiol. 16:1133–45 [Google Scholar]
124. Seidman D, Hebert KS, Truchan HK, Miller DP, Tegels BK. 124.  et al. 2015. Essential domains of Anaplasma phagocytophilum invasins utilized to infect mammalian host cells. PLOS Pathog. 11:e1004669 [Google Scholar]
125. Dark MJ, Al-Khedery B, Barbet AF. 125.  2011. Multistrain genome analysis identifies candidate vaccine antigens of Anaplasma marginale. Vaccine 29:4923–32 [Google Scholar]
126. Collins NE, Liebenberg J, de Villiers EP, Brayton KA, Louw E. 126.  et al. 2005. The genome of the heartwater agent Ehrlichia ruminantium contains multiple tandem repeats of actively variable copy number. PNAS 102:838–43 [Google Scholar]
127. Singu V, Peddireddi L, Sirigireddy KR, Cheng C, Munderloh U, Ganta RR. 127.  2006. Unique macrophage and tick cell-specific protein expression from the p28/p30-outer membrane protein multigene locus in Ehrlichia chaffeensis and Ehrlichia canis. Cell. Microbiol. 8:1475–87 [Google Scholar]
128. Van Heerden H, Collins NE, Brayton KA, Rademeyer C, Allsopp BA. 128.  2004. Characterization of a major outer membrane protein multigene family in Ehrlichia ruminantium. Gene 330:159–68 [Google Scholar]
129. Dumler JS. 129.  2005. Anaplasma and Ehrlichia infection. Ann. N.Y. Acad. Sci. 1063:361–73 [Google Scholar]
130. Stuen S. 130.  2007. Anaplasma phagocytophilum—the most widespread tick-borne infection in animals in Europe. Vet. Res. Commun. 31:Suppl. 179–84 [Google Scholar]
131. Chen SM, Dumler JS, Bakken JS, Walker DH. 131.  1994. Identification of a granulocytotropic Ehrlichia species as the etiologic agent of human disease. J. Clin. Microbiol 32:589–95 [Google Scholar]
132. Herron MJ, Ericson ME, Kurtti TJ, Munderloh UG. 132.  2005. The interactions of Anaplasma phagocytophilum, endothelial cells, and human neutrophils. Ann. N.Y. Acad. Sci. 1063:374–82 [Google Scholar]
133. Klein MB, Miller JS, Nelson CM, Goodman JL. 133.  1997. Primary bone marrow progenitors of both granulocytic and monocytic lineages are susceptible to infection with the agent of human granulocytic ehrlichiosis. J. Infect. Dis. 176:1405–9 [Google Scholar]
134. Stuen S, Granquist EG, Silaghi C. 134.  2013. Anaplasma phagocytophilum—a widespread multi-host pathogen with highly adaptive strategies. Front. Cell. Infect. Microbiol. 3:31 [Google Scholar]
135. Dumler JS, Madigan JE, Pusterla N, Bakken JS. 135.  2007. Ehrlichioses in humans: epidemiology, clinical presentation, diagnosis, and treatment. Clin. Infect. Dis. 45:Suppl. 1S45–S51 [Google Scholar]
136. Telford SR III, Dawson JE, Katavolos P, Warner CK, Kolbert CP, Persing DH. 136.  1996. Perpetuation of the agent of human granulocytic ehrlichiosis in a deer tick-rodent cycle. PNAS 93:6209–14 [Google Scholar]
137. Hodzic E, Ijdo JW, Feng S, Katavolos P, Sun W. 137.  et al. 1998. Granulocytic ehrlichiosis in the laboratory mouse. J. Infect. Dis. 177:737–45 [Google Scholar]
138. Alberdi MP, Walker AR, Paxton EA, Sumption KJ. 138.  1998. Natural prevalence of infection with Ehrlichia (Cytoecetes) phagocytophila of Ixodes ricinus ticks in Scotland. Vet. Parasitol. 78:203–13 [Google Scholar]
139. Greig A, Macleod NS, Allison CJ. 139.  1977. Tick borne fever in association with mucosal disease and cobalt deficiency in calves. Vet. Rec. 100:562–64 [Google Scholar]
140. Stuen S, Grova L, Granquist EG, Sandstedt K, Olesen I, Steinshamn H. 140.  2011. A comparative study of clinical manifestations, haematological and serological responses after experimental infection with Anaplasma phagocytophilum in two Norwegian sheep breeds. Acta Vet. Scand. 53:8 [Google Scholar]
141. Beall MJ, Chandrashekar R, Eberts MD, Cyr KE, Diniz PP. 141.  et al. 2008. Serological and molecular prevalence of Borrelia burgdorferi, Anaplasma phagocytophilum, and Ehrlichia species in dogs from Minnesota. Vector Borne Zoonotic Dis. 8:455–64 [Google Scholar]
142. Carrade DD, Foley JE, Borjesson DL, Sykes JE. 142.  2009. Canine granulocytic anaplasmosis: a review. J. Vet. Intern. Med. 23:1129–41 [Google Scholar]
143. Chastagner A, Dugat T, Vourc'h G, Verheyden H, Legrand L. 143.  et al. 2014. Multilocus sequence analysis of Anaplasma phagocytophilum reveals three distinct lineages with different host ranges in clinically ill French cattle. Vet. Res. 45:114 [Google Scholar]
144. Eberts MD, Vissotto de Paiva Diniz PP, Beall MJ, Stillman BA, Chandrashekar R, Breitschwerdt EB. 144.  2011. Typical and atypical manifestations of Anaplasma phagocytophilum infection in dogs. J. Am. Anim. Hosp. Assoc. 47:e86–e94 [Google Scholar]
145. Gokce HI, Genc O, Akca A, Vatansever Z, Unver A, Erdogan HM. 145.  2008. Molecular and serological evidence of Anaplasma phagocytophilum infection of farm animals in the Black Sea Region of Turkey. Acta Vet. Hung. 56:281–92 [Google Scholar]
146. Gorman JK, Hoar BR, Nieto NC, Foley JE. 146.  2012. Evaluation of Anaplasma phagocytophilum infection in experimentally inoculated sheep and determination of Anaplasma spp seroprevalence in 8 free-ranging sheep flocks in California and Oregon. Am. J. Vet. Res. 73:1029–34 [Google Scholar]
147. Guyot H, Ramery E, O'Grady L, Sandersen C, Rollin F. 147.  2011. Emergence of bovine ehrlichiosis in Belgian cattle herds. Ticks Tick-Borne Dis. 2:116–18 [Google Scholar]
148. Hilton H, Madigan JE, Aleman M. 148.  2008. Rhabdomyolysis associated with Anaplasma phagocytophilum infection in a horse. J. Vet. Intern. Med. 22:1061–64 [Google Scholar]
149. Lempereur L, Lebrun M, Cuvelier P, Sepult G, Caron Y. 149.  et al. 2012. Longitudinal field study on bovine Babesia spp. and Anaplasma phagocytophilum infections during a grazing season in Belgium. Parasitol. Res. 110:1525–30 [Google Scholar]
150. Madigan JE, Barlough JE, Dumler JS, Schankman NS, DeRock E. 150.  1996. Equine granulocytic ehrlichiosis in Connecticut caused by an agent resembling the human granulocytotropic ehrlichia. J. Clin. Microbiol. 34:434–35 [Google Scholar]
151. Madigan JE, Gribble D. 151.  1987. Equine ehrlichiosis in northern California: 49 cases (1968–1981). J. Am. Vet. Med. Assoc. 190:445–48 [Google Scholar]
152. Madigan JE, Hietala S, Chalmers S, DeRock E. 152.  1990. Seroepidemiologic survey of antibodies to Ehrlichia equi in horses of northern California. J. Am. Vet. Med. Assoc. 196:1962–64 [Google Scholar]
153. Madigan JE, Richter PJ Jr, Kimsey RB, Barlough JE, Bakken JS, Dumler JS. 153.  1995. Transmission and passage in horses of the agent of human granulocytic ehrlichiosis. J. Infect. Dis. 172:1141–44 [Google Scholar]
154. Matsumoto K, Joncour G, Davoust B, Pitel PH, Chauzy A. 154.  et al. 2006. Anaplasma phagocytophilum infection in cattle in France. Ann. N.Y. Acad. Sci. 1078:491–94 [Google Scholar]
155. Nieder M, Silaghi C, Hamel D, Pfister K, Schmaschke R, Pfeffer M. 155.  2012. Tick-borne fever caused by Anaplasma phagocytophilum in Germany: first laboratory confirmed case in a dairy cattle herd. Tierarztl. Prax. Ausg. G Grosstiere Nutztiere 40:101–6 [Google Scholar]
156. Plier ML, Young KM, Barlough JE, Madigan JE, Dumler JS. 156.  1999. Equine granulocytic ehrlichiosis: a case report with DNA analysis and species comparison. Vet. Clin. Pathol. 28:127–30 [Google Scholar]
157. Pusterla N, Anderson RJ, House JK, Pusterla JB, DeRock E, Madigan JE. 157.  2001. Susceptibility of cattle to infection with Ehrlichia equi and the agent of human granulocytic ehrlichiosis. J. Am. Vet. Med. Assoc. 218:1160–62 [Google Scholar]
158. Silaghi C, Scheuerle MC, Friche Passos LM, Thiel C, Pfister K. 158.  2011. PCR detection of Anaplasma phagocytophilum in goat flocks in an area endemic for tick-borne fever in Switzerland. Parasite 18:57–62 [Google Scholar]
159. Stuen S, Longbottom D. 159.  2011. Treatment and control of chlamydial and rickettsial infections in sheep and goats. Vet. Clin. N. Am. Food Anim. Pract. 27:213–33 [Google Scholar]
160. Torina A, Caracappa S. 160.  2007. Anaplasmosis in cattle in Italy. Vet. Res. Commun. 31:Suppl. 173–78 [Google Scholar]
161. Yang J, Liu Z, Guan G, Liu Q, Li Y. 161.  et al. 2013. Prevalence of Anaplasma phagocytophilum in ruminants, rodents and ticks in Gansu, northwestern China. J. Med. Microbiol. 62:254–58 [Google Scholar]
162. Granquist EG, Bårdsen K, Bergström K, Stuen S. 162.  2010. Variant and individual dependent nature of persistent Anaplasma phagocytophilum infection. Acta Vet. Scand. 52:25 [Google Scholar]
163. Stuen S, Bergström K, Petrovec M, Van de Pol I, Schouls LM. 163.  2003. Differences in clinical manifestations and hematological and serological responses after experimental infection with genetic variants of Anaplasma phagocytophilum in sheep. Clin. Diagn. Lab. Immunol. 10:692–95 [Google Scholar]
164. Woldehiwet Z. 164.  2010. The natural history of Anaplasma phagocytophilum. Vet. Parasitol. 167:108–22 [Google Scholar]
165. Akkoyunlu M, Fikrig E. 165.  2000. Gamma interferon dominates the murine cytokine response to the agent of human granulocytic ehrlichiosis and helps to control the degree of early rickettsemia. Infect. Immun. 68:1827–33 [Google Scholar]
166. Banerjee R, Anguita J, Fikrig E. 166.  2000. Granulocytic ehrlichiosis in mice deficient in phagocyte oxidase or inducible nitric oxide synthase. Infect. Immun. 68:4361–62 [Google Scholar]
167. Banerjee R, Anguita J, Roos D, Fikrig E. 167.  2000. Cutting edge: Infection by the agent of human granulocytic ehrlichiosis prevents the respiratory burst by down-regulating gp91^phox. J. Immunol. 164:3946–49 [Google Scholar]
168. Martin ME, Bunnell JE, Dumler JS. 168.  2000. Pathology, immunohistology, and cytokine responses in early phases of human granulocytic ehrlichiosis in a murine model. J. Infect. Dis. 181:374–78 [Google Scholar]
169. Martin ME, Caspersen K, Dumler JS. 169.  2001. Immunopathology and ehrlichial propagation are regulated by interferon-γ and interleukin-10 in a murine model of human granulocytic ehrlichiosis. Am. J. Pathol. 158:1881–88 [Google Scholar]
170. Sun W, Ijdo JW, Telford SR III, Hodzic E, Zhang Y. 170.  et al. 1997. Immunization against the agent of human granulocytic ehrlichiosis in a murine model. J. Clin. Investig. 100:3014–18 [Google Scholar]
171. Dumler JS, Trigiani ER, Bakken JS, Aguero-Rosenfeld ME, Wormser GP. 171.  2000. Serum cytokine responses during acute human granulocytic ehrlichiosis. Clin. Diagn. Lab. Immunol. 7:6–8 [Google Scholar]
172. Woldehiwet Z. 172.  2008. Immune evasion and immunosuppression by Anaplasma phagocytophilum, the causative agent of tick-borne fever of ruminants and human granulocytic anaplasmosis. Vet. J. 175:37–44 [Google Scholar]
173. Gokce HI, Woldehiwet Z. 173.  1999. Differential haematological effects of tick-borne fever in sheep and goats. Zentralbl. Veterinarmed. B 46:105–15 [Google Scholar]
174. Taylor AW, Holman HH, Gordon WS. 174.  1941. Attempts to reproduce the pyaemia associated with tick bite. Vet. Rec. 53:339–44 [Google Scholar]
175. Woldehiwet Z. 175.  1987. The effects of tick-borne fever on some functions of polymorphonuclear cells of sheep. J. Comp. Pathol. 97:481–85 [Google Scholar]
176. Borjesson DL, Kobayashi SD, Whitney AR, Voyich JM, Argue CM, Deleo FR. 176.  2005. Insights into pathogen immune evasion mechanisms: Anaplasma phagocytophilum fails to induce an apoptosis differentiation program in human neutrophils. J. Immunol. 174:6364–72 [Google Scholar]
177. Carlyon JA, Chan WT, Galan J, Roos D, Fikrig E. 177.  2002. Repression of rac2 mRNA expression by Anaplasma phagocytophila is essential to the inhibition of superoxide production and bacterial proliferation. J. Immunol. 169:7009–18 [Google Scholar]
178. Mott J, Rikihisa Y. 178.  2000. Human granulocytic ehrlichiosis agent inhibits superoxide anion generation by human neutrophils. Infect. Immun. 68:6697–703 [Google Scholar]
179. Wang T, Malawista SE, Pal U, Grey M, Meek J. 179.  et al. 2002. Superoxide anion production during Anaplasma phagocytophila infection. J. Infect. Dis. 186:274–80 [Google Scholar]
180. Whist SK, Storset AK, Larsen HJ. 180.  2002. Functions of neutrophils in sheep experimentally infected with Ehrlichia phagocytophila. Vet. Immunol. Immunopathol. 86:183–93 [Google Scholar]
181. Whist SK, Storset AK, Johansen GM, Larsen HJ. 181.  2003. Modulation of leukocyte populations and immune responses in sheep experimentally infected with Anaplasma (formerly Ehrlichia) phagocytophilum. Vet. Immunol. Immunopathol. 94:163–75 [Google Scholar]
182. Woldehiwet Z. 182.  1987. Depression of lymphocyte response to mitogens in sheep infected with tick-borne fever. J. Comp. Pathol. 97:637–43 [Google Scholar]
183. Batungbacal MR, Scott GR. 183.  1982. Suppression of the immune response to clostridial vaccine by tick-borne fever. J. Comp. Pathol. 92:409–13 [Google Scholar]
184. Batungbacal MR, Scott GR. 184.  1982. Tick-borne fever and concurrent parainfluenza-3 virus infection in sheep. J. Comp. Pathol. 92:415–28 [Google Scholar]
185. Gokce HI, Woldehiwet Z. 185.  1999. Lymphocyte responses to mitogens and rickettsial antigens in sheep experimentally infected with Ehrlichia (Cytoecetes) phagocytophila. Vet. Parasitol. 83:55–64 [Google Scholar]
186. Batungbacal MR, Scott GR, Burrells C. 186.  1982. The lymphocytopaenia in tick-borne fever. J. Comp. Pathol. 92:403–7 [Google Scholar]
187. Woldehiwet Z. 187.  1991. Lymphocyte subpopulations in peripheral blood of sheep experimentally infected with tick-borne fever. Res. Vet. Sci. 51:40–43 [Google Scholar]