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Review

Progress and obstacles in vaccine development for the ehrlichioses

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Pages 1071-1082 | Published online: 09 Jan 2014

References

  • Provost A, Bezuidenhout JD. The historical background and global importance of heartwater. Onderstepoort J. Vet. Res.54(3), 165–169 (1987).
  • Huxsoll DL, Hildebrandt PK, Nims RM, Ferguson JA, Walker JS. Ehrlichia canis– the causative agent of a haemorrhagic disease of dogs? Vet. Rec.85, 587 (1969).
  • Maeda K, Markowitz N, Hawley RC, Ristic M, Cox D, McDade JE. Human infection with Ehrlichia canis, a leukocytic rickettsia. N. Engl. J. Med.316, 853–856 (1987).
  • Buller RS, Arens M, Hmiel SP et al.Ehrlichia ewingii, a newly recognized agent of human ehrlichiosis. N. Engl. J. Med.341(3), 148–155 (1999).
  • Perez M, Bodor M, Zhang C, Xiong Q, Rikihisa Y. Human infection with Ehrlichia canis accompanied by clinical signs in Venezuela. Ann. NY Acad. Sci.1078, 110–117 (2006).
  • McQuiston JH, Paddock CD, Holman RC, Childs JE. Human ehrlichioses in the United States. Emerg. Infect. Dis.5(5), 635–642 (1999).
  • Paddock CD, Folk SM, Shore GM et al. Infections with Ehrlichia chaffeensis and Ehrlichia ewingii in persons coinfected with human immunodeficiency virus. Clin. Infect. Dis.33(9), 1586–1594 (2001).
  • Perez M, Rikihisa Y, Wen B. Ehrlichia canis-like agent isolated from a man in Venezuela: antigenic and genetic characterization. J. Clin. Microbiol.34(9), 2133–2139 (1996).
  • Neitz W, Alexander RA. Immunization of cattle against heartwater and the control of the tick-borne diseases, red-water, gallsickness and heartwater. Onderstepoort J. Vet. Res.20, 137–158 (1945).
  • Allsopp BA. Trends in the control of heartwater. Onderstepoort J. Vet. Res.76(1), 81–88 (2009).
  • Allsopp BA. Natural history of Ehrlichia ruminantium. Vet. Parasitol.167(2–4), 123–135 (2010).
  • Anderson BE, Sumner JW, Dawson JE et al. Detection of the etiologic agent of human ehrlichiosis by polymerase chain reaction. J. Clin. Microbiol.30(4), 775–780 (1992).
  • Eng TR, Harkess JR, Fishbein DB et al. Epidemiologic, clinical, and laboratory findings of human ehrlichiosis in the United States, 1988. J. Am. Med. Assoc.264(17), 2251–2258 (1990).
  • Fishbein DB, Dawson JE, Robinson LE. Human ehrlichiosis in the United States, 1985 to 1990. Ann. Intern. Med.120(9), 736–743 (1994).
  • Paddock CD, Childs JE. Ehrlichia chaffeensis: a prototypical emerging pathogen. Clin. Microbiol. Rev.16(1), 37–64 (2003).
  • Childs JE, Paddock CD. The ascendancy of Amblyomma americanum as a vector of pathogens affecting humans in the United States. Annu. Rev. Entomol.48, 307–337 (2003).
  • Goldman EE, Breitschwerdt EB, Grindem CB, Hegarty BC, Walls JJ, Dumler JS. Granulocytic ehrlichiosis in dogs from North Carolina and Virginia. J. Vet. Intern. Med.12(2), 61–70 (1998).
  • Anziani OS, Ewing SA, Barker RW. Experimental transmission of a granulocytic form of the tribe Ehrlichieae by Dermacentor variabilis and Amblyomma americanum to dogs. Am. J. Vet. Res.51(6), 929–931 (1990).
  • Uilenberg G. Heartwater (Cowdria ruminantium infection): current status. Adv. Vet. Sci. Comp. Med.27, 427–480 (1983).
  • Mahan SM, Peter TF, Simbi BH et al. Comparison of efficacy of American and African Amblyomma ticks as vectors of heartwater (Cowdria ruminantium) infection by molecular analyses and transmission trials. J. Parasitol.86(1), 44–49 (2000).
  • Barre N, Uilenberg G, Morel PC, Camus E. Danger of introducing heartwater onto the American mainland: potential role of indigenous and exotic Amblyomma ticks. Onderstepoort J. Vet. Res.54(3), 405–417 (1987).
  • Uilenberg G. Experimental transmission of Cowdria ruminantium by the Gulf coast tick Amblyomma maculatum: danger of introducing heartwater and benign African theileriasis onto the American mainland. Am. J. Vet. Res.43(7), 1279–1282 (1982).
  • Burridge MJ, Simmons LA, Peter TF, Mahan SM. Increasing risks of introduction of heartwater onto the American mainland associated with animal movements. Ann. NY Acad. Sci.969, 269–274 (2002).
  • Burridge MJ, Simmons LA, Simbi BH, Mahan SM, Fournier PE, Raoult D. Introduction of the exotic tick Amblyomma hebraeum into Florida on a human host. J. Parasitol.88(4), 800–801 (2002).
  • Burridge MJ, Simmons LA, Simbi BH, Peter TF, Mahan SM. Evidence of Cowdria ruminantium infection (heartwater) in Amblyomma sparsum ticks found on tortoises imported into Florida. J. Parasitol.86(5), 1135–1136 (2000).
  • Loftis AD, Mixson TR, Stromdahl EY et al. Geographic distribution and genetic diversity of the Ehrlichia sp. from Panola Mountain in Amblyomma americanum. BMC Infect. Dis.8, 54 (2008).
  • Yabsley MJ, Loftis AD, Little SE. Natural and experimental infection of white-tailed deer (Odocoileus virginianus) from the United States with an Ehrlichia sp. closely related to Ehrlichia ruminantium. J. Wildl. Dis.44(2), 381–387 (2008).
  • Keefe TJ, Holland CJ, Salyer PE, Ristic M. Distribution of Ehrlichia canis among military working dogs in the world and selected civilian dogs in the United States. J. Am. Vet. Med. Assoc.181, 236–238 (1982).
  • Groves MG, Dennis GL, Amyx HL, Huxsoll DL. Transmission of Ehrlichia canis to dogs by ticks (Rhipicephalus sanguineus). Am. J. Vet. Res.36, 937–940 (1975).
  • Harrus S, Waner T, Aizenberg I, Foley JE, Poland AM, Bark H. Amplification of Ehrlichial DNA from dogs 34 months after infection with Ehrlichia canis. J. Clin. Microbiol.36(1), 73–76 (1998).
  • Breitschwerdt EB, Hegarty BC, Hancock SI. Doxycycline hyclate treatment of experimental canine ehrlichiosis followed by challenge inoculation with two Ehrlichia canis strains. Antimicrob. Agents Chemother.42(2), 362–368 (1998).
  • van der Merwe L. The infection and treatment method of vaccination against heartwater. Onderstepoort J. Vet. Res.54(3), 489–491 (1987).
  • Bitsaktsis C, Huntington J, Winslow G. Production of IFN-γ by CD4 T cells is essential for resolving Ehrlichia infection. J. Immunol.172(11), 6894–6901 (2004).
  • Totte P, McKeever D, Martinez D, Bensaid A. Analysis of T-cell responses in cattle immunized against heartwater by vaccination with killed elementary bodies of Cowdria ruminantium. Infect. Immun.65(1), 236–241 (1997).
  • Byrom B, Mahan SM, Barbet AF. The development of antibody to Cowdria ruminantium in mice and its role in heartwater disease. Rev. Elev. Med. Vet. Pays Trop.46(1–2), 197–201 (1993).
  • du Plessis JL. Immunity in heartwater. I. A preliminary note on the role of serum antibodies. Onderstepoort J. Vet. Res.37(3), 147–149 (1970).
  • Winslow GM, Yager E, Shilo K, Volk E, Reilly A, Chu FK. Antibody-mediated elimination of the obligate intracellular bacterial pathogen Ehrlichia chaffeensis during active infection. Infect. Immun.68(4), 2187–2195 (2000).
  • Yager E, Bitsaktsis C, Nandi B, McBride JW, Winslow G. Essential role for humoral immunity during Ehrlichia infection in immunocompetent mice. Infect. Immun.73(12), 8009–8016 (2005).
  • Feng HM, Walker DH. Mechanisms of immunity to Ehrlichia muris: a model of monocytotropic ehrlichiosis. Infect. Immun.72(2), 966–971 (2004).
  • Collins NE, Liebenberg J, de Villiers EP et al. The genome of the heartwater agent Ehrlichia ruminantium contains multiple tandem repeats of actively variable copy number. Proc. Natl Acad. Sci. USA102(3), 838–843 (2005).
  • Frutos R, Viari A, Ferraz C et al. Comparative genomic analysis of three strains of Ehrlichia ruminantium reveals an active process of genome size plasticity. J. Bacteriol.188(7), 2533–2542 (2006).
  • Allsopp MT, Allsopp BA. Extensive genetic recombination occurs in the field between different genotypes of Ehrlichia ruminantium. Vet. Microbiol.124(1–2), 58–65 (2007).
  • Faburay B, Jongejan F, Taoufik A, Ceesay A, Geysen D. Genetic diversity of Ehrlichia ruminantium in Amblyomma variegatum ticks and small ruminants in The Gambia determined by restriction fragment profile analysis. Vet. Microbiol.126(1–3), 189–199 (2008).
  • Barbet AF, Byrom B, Mahan SM. Diversity of Ehrlichia ruminantium major antigenic protein 1–2 in field isolates and infected sheep. Infect. Immun.77(6), 2304–2310 (2009).
  • Allsopp B, McBride JW. Ehrlichia. In: Genome Mapping and Genomics in Animal-Associated Microbes. Nene V, Kole C (Eds). Springer Verlag, Berlin/Heidelberg, Germany, 117–164 (2009).
  • Adakal H, Meyer DF, Carasco-Lacombe C et al. MLST scheme of Ehrlichia ruminantium: genomic stasis and recombination in strains from Burkina-Faso. Infect. Genet. Evol.9(6), 1320–1328 (2009).
  • Allsopp MT, Dorfling CM, Maillard JC et al.Ehrlichia ruminantium major antigenic protein gene (map1) variants are not geographically constrained and show no evidence of having evolved under positive selection pressure. J. Clin. Microbiol.39(11), 4200–4203 (2001).
  • Raliniaina M, Meyer DF, Pinarello V et al. Mining the genetic diversity of Ehrlichia ruminantium using map genes family. Vet. Parasitol.167(2–4), 187–195 (2010).
  • Yu XJ, McBride JW, Walker DH. Genetic diversity of the 28-kilodalton outer membrane protein gene in human isolates of Ehrlichia chaffeensis.J. Clin. Microbiol.37(4), 1137–1143 (1999).
  • Doyle CK, Cardenas AM, Aguiar DM et al. Molecular characterization of E. canis gp36 and E. chaffeensis gp47 tandem repeats among different geographic locations. Ann. NY Acad. Sci.1063, 433–435 (2006).
  • Standaert SM, Yu T, Scott MA et al. Primary isolation of Ehrlichia chaffeensis from patients with febrile illnesses: clinical and molecular characteristics. J. Infect. Dis.181(3), 1082–1088 (2000).
  • Sumner JW, Childs JE, Paddock CD. Molecular cloning and characterization of the Ehrlichia chaffeensis variable-length PCR target: an antigen-expressing gene that exhibits interstrain variation. J. Clin. Microbiol.37(5), 1447–1453 (1999).
  • Cheng C, Paddock CD, Reddy GR. Molecular heterogeneity of Ehrlichia chaffeensis isolates determined by sequence analysis of the 28-kilodalton outer membrane protein genes and other regions of the genome. Infect. Immun.71(1), 187–195 (2003).
  • Long SW, Zhang XF, Qi H, Standaert S, Walker DH, Yu XJ. Antigenic variation of Ehrlichia chaffeensis resulting from differential expression of the 28-kilodalton protein gene family. Infect. Immun.70(4), 1824–1831 (2002).
  • Zhang X, Luo T, Keysary A et al. Genetic and antigenic diversities of major immunoreactive proteins in globally distributed Ehrlichia canis strains. Clin. Vaccine Immunol.15(7), 1080–1088 (2008).
  • McBride JW, Yu X, Walker DH. A conserved, transcriptionally active p28 multigene locus of Ehrlichia canis. Gene254(1–2), 245–252 (2000).
  • Yu XJ, McBride JW, Diaz CM, Walker DH. Molecular cloning and characterization of the 120-kilodalton protein gene of Ehrlichia canis and application of the recombinant 120-kilodalton protein for serodiagnosis of canine ehrlichiosis. J. Clin. Microbiol.38(1), 369–374 (2000).
  • McBride JW, Doyle CK, Zhang X et al. Identification of a glycosylated Ehrlichia canis 19-kDa major immunoreactive protein with a species-specific serine-rich glycopeptide epitope. Infect. Immun.75(1), 74–82 (2006).
  • Barbet AF, Whitmire WM, Kamper SM et al. A subset of Cowdria ruminantium genes important for immune recognition and protection. Gene275(2), 287–298 (2001).
  • Pretorius A, Van Strijp F, Brayton KA, Collins NE, Allsopp BA. Genetic immunization with Ehrlichia ruminantium GroEL and GroES homologues. Ann. NY Acad. Sci.969, 151–154 (2002).
  • Louw E, Brayton KA, Collins NE, Pretorius A, Van Strijp F, Allsopp BA. Sequencing of a 15-kb Ehrlichia ruminantium clone and evaluation of the cpg1 open reading frame for protection against heartwater. Ann. NY Acad. Sci.969, 147–150 (2002).
  • Collins NE, Pretorius A, van Kleef M et al. Development of improved attenuated and nucleic acid vaccines for heartwater. Dev. Biol. (Basel)114, 121–136 (2003).
  • Winslow GM, Yager E, Shilo K, Collins DN, Chu FK. Infection of the laboratory mouse with the intracellular pathogen Ehrlichia chaffeensis. Infect. Immun.66(8), 3892–3899 (1998).
  • Bitsaktsis C, Nandi B, Racine R, MacNamara KC, Winslow G. T-cell-independent humoral immunity is sufficient for protection against fatal intracellular Ehrlichia infection. Infect. Immun.75(10), 4933–4941 (2007).
  • Sotomayor E, Popov VL, Feng HM, Walker DH, Olano JP. Animal model of fatal human monocytotropic ehrlichiosis. Am. J. Path.158, 757–769 (2001).
  • Winslow GM, Bitsaktsis C, Yager E. Susceptibility and resistance to monocytic ehrlichiosis in the mouse. Ann. NY Acad. Sci.1063, 395–402 (2005).
  • Ismail N, Soong L, McBride JW et al. Overproduction of TNF-α by CD8+ type 1 cells and down-regulation of IFN-γ production by CD4+ Th1 cells contribute to toxic shock-like syndrome in an animal model of fatal monocytotropic ehrlichiosis. J. Immunol.172(3), 1786–1800 (2004).
  • Ismail N, Stevenson HL, Walker DH. Role of tumor necrosis factor a (TNF-α) and interleukin-10 in the pathogenesis of severe murine monocytotropic ehrlichiosis: increased resistance of TNF receptor p55- and p75-deficient mice to fatal Ehrlichial infection. Infect. Immun.74(3), 1846–1856 (2006).
  • Pretorius A, van Kleef M, Collins NE et al. A heterologous prime/boost immunisation strategy protects against virulent E. ruminantium Welgevonden needle challenge but not against tick challenge. Vaccine26(34), 4363–4371 (2008).
  • Singu V, Liu H, Cheng C, Ganta RR. Ehrlichia chaffeensis expresses macrophage- and tick cell-specific 28-kilodalton outer membrane proteins. Infect. Immun.73(1), 79–87 (2005).
  • Singu V, Peddireddi L, Sirigireddy KR, Cheng C, Munderloh U, Ganta RR. 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(9), 1475–1487 (2006).
  • Unver A, Ohashi N, Tajima T, Stich RW, Grover D, Rikihisa Y. Transcriptional analysis of p30 major outer membrane multigene family of Ehrlichia canis in dogs, ticks, and cell culture at different temperatures. Infect. Immun.69(10), 6172–6178 (2001).
  • Postigo M, Taoufik A, Bell-Sakyi L et al. Host cell-specific protein expression in vitro in Ehrlichia ruminantium.Vet. Microbiol.128(1–2), 136–147 (2008).
  • Bekker CP, Postigo M, Taoufik A et al. Transcription analysis of the major antigenic protein 1 multigene family of three in vitro-cultured Ehrlichia ruminantium isolates. J. Bacteriol.187(14), 4782–4791 (2005).
  • Postigo M, Taoufik A, Bell-Sakyi L, de Vries E, Morrison WI, Jongejan F. Differential transcription of the major antigenic protein 1 multigene family of Ehrlichia ruminantium in Amblyomma variegatum ticks. Vet. Microbiol.122(3–4), 298–305 (2007).
  • Ganta RR, Cheng C, Miller EC et al. Differential clearance and immune responses to tick cell-derived versus macrophage culture-derived Ehrlichia chaffeensis in mice. Infect. Immun.75(1), 135–145 (2007).
  • Kuriakose JA, Zhu B, McBride JW. Transcriptomic analysis of Ehrlichia chaffeensis in the mononuclear phagocyte reveals two tandem repeat proteins are hyper-expressed. Presented at: 23rd Meeting of the American Society for Rickettsiology. Crowne Plaza Resort, SC, USA, 15–18 August (2009).
  • Allsopp MT, van Strijp MF, Faber E, Josemans AI, Allsopp BA. Ehrlichia ruminantium variants which do not cause heartwater found in South Africa. Vet. Microbiol.120(1–2), 158–166 (2007).
  • Miura K, Rikihisa Y. Virulence potential of Ehrlichia chaffeensis strains of distinct genome sequences. Infect. Immun.75(7), 3604–3613 (2007).
  • Miura K, Rikihisa Y. Liver transcriptome profiles associated with strain-specific Ehrlichia chaffeensis-induced hepatitis in SCID mice. Infect. Immun.77(1), 245–254 (2009).
  • Paddock CD, Sumner JW, Shore GM et al. Isolation and characterization of Ehrlichia chaffeensis strains from patients with fatal ehrlichiosis. J. Clin. Microbiol.35(10), 2496–2502 (1997).
  • Yu XJ, Crocquet-Valdes P, Walker DH. Cloning and sequencing of the gene for a 120-kDa immunodominant protein of Ehrlichia chaffeensis.Gene184(2), 149–154 (1997).
  • Doyle CK, Nethery KA, Popov VL, McBride JW. Differentially expressed and secreted major immunoreactive protein orthologs of Ehrlichia canis and E. chaffeensis elicit early antibody responses to epitopes on glycosylated tandem repeats. Infect. Immun.74(1), 711–720 (2006).
  • McBride JW, Comer JE, Walker DH. Novel immunoreactive glycoprotein orthologs of Ehrlichia spp. Ann. NY Acad. Sci.990, 678–684 (2003).
  • Luo T, Zhang X, Wakeel A, Popov VL, McBride JW. A variable-length PCR target protein of Ehrlichia chaffeensis contains major species-specific antibody epitopes in acidic serine-rich tandem repeats. Infect. Immun.76(4), 1572–1580 (2008).
  • Luo T, Zhang X, McBride JW. Major species-specific antibody epitopes of the Ehrlichia chaffeensis p120 and E. canis p140 orthologs in surface-exposed tandem repeat regions. Clin. Vaccine Immunol.16(7), 982–990 (2009).
  • Luo T, Zhang X, Nicholson WL, Zhu B, McBride JW. Molecular characterization of antibody epitopes of Ehrlichia chaffeensis ankyrin protein 200 and tandem repeat protein 47 and evaluation of synthetic immunodeterminants for serodiagnosis of human monocytotropic ehrlichiosis. Clin. Vaccine Immunol.17(1), 87–97 (2010).
  • Nethery KA, Doyle CK, Zhang X, McBride JW. Ehrlichia canis gp200 contains dominant species-specific antibody epitopes in terminal acidic domains. Infect. Immun.75, 4900–4908 (2007).
  • Chen SM, Dumler JS, Feng HM, Walker DH. Identification of the antigenic constituents of Ehrlichia chaffeensis. Am. J. Trop. Med. Hyg.50, 52–58 (1994).
  • Rikihisa Y, Ewing SA, Fox JC. Western immunoblot analysis of Ehrlichia chaffeensis, E. canis, or E. ewingii infections in dogs and humans. J. Clin. Microbiol.32, 2107–2112 (1994).
  • McBride JW, Corstvet RE, Gaunt SD, Boudreaux C, Guedry T, Walker DH. Kinetics of antibody response to Ehrlichia canis immunoreactive proteins. Infect. Immun.71, 2516–2524 (2003).
  • Mahan SM, McGuire TC, Semu SM et al. Molecular cloning of a gene encoding the immunogenic 21 kDa protein of Cowdria ruminantium.Microbiology140(Pt 8), 2135–2142 (1994).
  • Sulsona CR, Mahan SM, Barbet AF. The map1 gene of Cowdria ruminantium is a member of a multigene family containing both conserved and variable genes. Biochem. Biophys. Res. Commun.257, 300–305 (1999).
  • Jongejan F, Thielemans MJ. Identification of an immunodominant antigenically conserved 32-kilodalton protein from Cowdria ruminantium.Infect. Immun.57(10), 3243–3246 (1989).
  • Alleman AR, Barbet AF, Bowie MV, Sorenson HL, Wong SJ, Belanger M. Expression of a gene encoding the major antigenic protein 2 homolog of Ehrlichia chaffeensis and potential application for serodiagnosis. J. Clin. Microbiol.38(10), 3705–3709 (2000).
  • Knowles TT, Alleman AR, Sorenson HL et al. Characterization of the major antigenic protein 2 of Ehrlichia canis and Ehrlichia chaffeensis and its application for serodiagnosis of ehrlichiosis. Clin. Diagn. Lab. Immunol.10(4), 520–524 (2003).
  • Mwangi DM, McKeever DJ, Nyanjui JK, Barbet AF, Mahan SM. Major antigenic proteins 1 and 2 of Cowdria ruminantium are targets for T-lymphocyte responses of immune cattle. Ann. NY Acad. Sci.849, 372–374 (1998).
  • Mwangi DM, McKeever DJ, Nyanjui JK, Barbet AF, Mahan SM. Immunisation of cattle against heartwater by infection with Cowdria ruminantium elicits T lymphocytes that recognise major antigenic proteins 1 and 2 of the agent. Vet. Immunol. Immunopathol.85(1–2), 23–32 (2002).
  • Mahan SM, Tebele N, Mukwedeya D et al. An immunoblotting diagnostic assay for heartwater based on the immunodominant 32-kilodalton protein of Cowdria ruminantium detects false positives in field sera. J. Clin. Microbiol.31(10), 2729–2737 (1993).
  • Ohashi N, Zhi N, Zhang Y, Rikihisa Y. Immunodominant major outer membrane proteins of Ehrlichia chaffeensis are encoded by a polymorphic multigene family. Infect. Immun.66(1), 132–139 (1998).
  • Chen SM, Cullman LC, Walker DH. Western immunoblotting analysis of the antibody responses of patients with human monocytotropic ehrlichiosis to different strains of Ehrlichia chaffeensis and Ehrlichia canis. Clin. Diag. Lab. Immunol.4(6), 731–735 (1997).
  • Nandi B, Hogle K, Vitko N, Winslow GM. CD4 T-cell epitopes associated with protective immunity induced following vaccination of mice with an Ehrlichial variable outer membrane protein. Infect. Immun.75(11), 5453–5459 (2007).
  • Pretorius A, Collins NE, Steyn HC, van Strijp F, van KM, Allsopp BA. Protection against heartwater by DNA immunisation with four Ehrlichia ruminantium open reading frames. Vaccine25(12), 2316–2324 (2007).
  • van Kleef M, Macmillan H, Gunter NJ et al. Low molecular weight proteins of Cowdria ruminantium (Welgevonden isolate) induce bovine CD4+-enriched T-cells to proliferate and produce interferon-γ. Vet. Microbiol.85(3), 259–273 (2002).
  • Byrom B, Barbet AF, Obwolo M, Mahan SM. CD8(+) T cell knockout mice are less susceptible to Cowdria ruminantium infection than athymic, CD4(+) T cell knockout, and normal C57BL/6 mice. Vet. Parasitol.93(2), 159–172 (2000).
  • Byrom B, Obwolo M, Barbet AF, Mahan SM. A polarized Th1 type immune response to Cowdria ruminantium infection is detected in immune DBA/2 mice. J. Parasitol.86(5), 983–992 (2000).
  • Mwangi DM, Mahan SM, Nyanjui JK, Taracha EL, McKeever DJ. Immunization of cattle by infection with Cowdria ruminantium elicits T lymphocytes that recognize autologous, infected endothelial cells and monocytes. Infect. Immun.66(5), 1855–1860 (1998).
  • Mwangi DM, McKeever DJ, Mahan SM. Cellular immune responses of cattle to Cowdria ruminantium. Dev. Biol. Stand.92, 309–315 (1998).
  • du Plessis JL, Berche P, Van Gas L. T cell-mediated immunity to Cowdria ruminantium in mice: the protective role of Lyt-2+ T cells. Onderstepoort J. Vet. Res.58(3), 171–179 (1991).
  • Esteves I, Walravens K, Vachiery N, Martinez D, Letesson JJ, Totte P. Protective killed Ehrlichia ruminantium vaccine elicits IFN-γ responses by CD4+ and CD8+ T lymphocytes in goats. Vet. Immunol. Immunopathol.98(1–2), 49–57 (2004).
  • Totte P, Vachiery N, Martinez D et al. Recombinant bovine interferon γ inhibits the growth of Cowdria ruminantium but fails to induce major histocompatibility complex class II following infection of endothelial cells. Vet. Immunol. Immunopathol.53(1–2), 61–71 (1996).
  • Totte P, Blankaert D, Zilimwabagabo P, Werenne J. Inhibition of Cowdria ruminantium infectious yield by interferons α and γ in endothelial cells. Rev. Elev. Med. Vet. Pays Trop.46(1–2), 189–194 (1993).
  • Mahan SM, Sileghem M, Smith GE, Byrom B. Neutralization of bovine concanavalin-A T cell supernatant-mediated anti-Cowdria ruminantium activity with antibodies specific to interferon γ but not to tumor necrosis factor. Parasite Immunol.18(6), 317–324 (1996).
  • Mahan SM, Smith GE, Byrom B. Conconavalin A-stimulated bovine T-cell supernatants inhibit growth of Cowdria ruminantium in bovine endothelial cells in vitro. Infect. Immun.62(2), 747–750 (1994).
  • Mutunga M, Preston PM, Sumption KJ. Nitric oxide is produced by Cowdria ruminantium-infected bovine pulmonary endothelial cells in vitro and is stimulated by γ interferon. Infect. Immun.66(5), 2115–2121 (1998).
  • Esteves I, Vachiery N, Martinez D, Totte P. Analysis of Ehrlichia ruminantium-specific T1/T2 responses during vaccination with a protective killed vaccine and challenge of goats. Parasite Immunol.26(2), 95–103 (2004).
  • Ganta RR, Wilkerson MJ, Cheng C, Rokey AM, Chapes SK. Persistent Ehrlichia chaffeensis infection occurs in the absence of functional major histocompatibility complex class II genes. Infect. Immun.70(1), 380–388 (2002).
  • Stevenson HL, Jordan JM, Peerwani Z, Wang HQ, Walker DH, Ismail N. An intradermal environment promotes a protective type-1 response against lethal systemic monocytotropic ehrlichial infection. Infect. Immun.74(8), 4856–4864 (2006).
  • Li JS, Chu F, Reilly A, Winslow GM. Antibodies highly effective in SCID mice during infection by the intracellular bacterium Ehrlichia chaffeensis are of picomolar affinity and exhibit preferential epitope and isotype utilization. J. Immunol.169(3), 1419–1425 (2002).
  • Li JS, Yager E, Reilly M et al. Outer membrane protein-specific monoclonal antibodies protect SCID mice from fatal infection by the obligate intracellular bacterial pathogen Ehrlichia chaffeensis.J. Immunol.166(3), 1855–1862 (2001).
  • Lee EH, Rikihisa Y. Anti-Ehrlichia chaffeensis antibody complexed with E. chaffeensis induces potent proinflammatory cytokine mRNA expression in human monocytes through sustained reduction of IκB-α and activation of NF-κB. Infect. Immun.65(7), 2890–2897 (1997).
  • du Plessis JL. Colostrum-derived antibodies to Cowdria ruminantium in the serum of calves and lambs. Onderstepoort J. Vet. Res.51(4), 275–276 (1984).
  • Fichtenbaum CJ, Peterson LR, Weil GJ. Ehrlichiosis presenting as a life-threatening illness with features of the toxic shock syndrome. Am. J. Med.95(4), 351–357 (1993).
  • Ismail N, Crossley EC, Stevenson HL, Walker DH. Relative importance of T-cell subsets in monocytotropic ehrlichiosis: a novel effector mechanism involved in Ehrlichia-induced immunopathology in murine ehrlichiosis. Infect. Immun.75(9), 4608–4620 (2007).
  • Bitsaktsis C, Winslow G. Fatal recall responses mediated by CD8 T cells during intracellular bacterial challenge infection. J. Immunol.177(7), 4644–4651 (2006).
  • Thirumalapura NR, Stevenson HL, Walker DH, Ismail N. Protective heterologous immunity against fatal ehrlichiosis and lack of protection following homologous challenge. Infect. Immun.76(5), 1920–1930 (2008).
  • Stevenson HL, Crossley EC, Thirumalapura N, Walker DH, Ismail N. Regulatory roles of CD1D-restricted NKT cells in the induction of toxic shock-like syndrome in an animal model of fatal ehrlichiosis. Infect. Immun.76(4), 1434–1444 (2008).
  • Wakeel A, Zhu B, Yu XJ, McBride JW. New insights into molecular Ehrlichia chaffeensis–host interactions. Microbes Infect.12(5), 337–345 (2010).
  • Zhang JZ, Sinha M, Luxon BA, Yu XJ. Survival strategy of obligately intracellular Ehrlichia chaffeensis: novel modulation of immune response and host cell cycles. Infect. Immun.72(1), 498–507 (2004).
  • Wakeel A, Kuriakose JA, McBride JW. An Ehrlichia chaffeensis tandem repeat protein interacts with multiple host targets involved in cell signaling, transcriptional regulation, and vesicle trafficking. Infect. Immun.77(5), 1734–1745 (2009).
  • Lee EH, Rikihisa Y. Protein kinase A-mediated inhibition of γ interferon-induced tyrosine phosphorylation of Janus kinases and latent cytoplasmic transcription factors in human monocytes by Ehrlichia chaffeensis.Infect. Immun.66(6), 2514–2520 (1998).
  • Kumagai Y, Cheng Z, Lin M, Rikihisa Y. Biochemical activities of three pairs of Ehrlichia chaffeensis two-component regulatory system proteins involved in inhibition of lysosomal fusion. Infect. Immun.74(9), 5014–5022 (2006).
  • Xiong Q, Bao W, Ge Y, Rikihisa Y. Ehrlichia ewingii infection delays spontaneous neutrophil apoptosis through stabilization of mitochondria. J. Infect. Dis.197(8), 1110–1118 (2008).
  • Dunning Hotopp JC, Lin M, Madupu R et al. Comparative genomics of emerging human ehrlichiosis agents. PLoS Genet.2(2), e21 (2006).
  • Mavromatis K, Doyle CK, Lykidis A et al. The genome of the obligately intracellular bacterium Ehrlichia canis reveals themes of complex membrane structure and immune evasion strategies. J. Bacteriol.188(11), 4015–4023 (2006).
  • Frutos R, Viari A, Ferraz C et al. Comparative genomics of three strains of Ehrlichia ruminantium: a review. Ann. NY Acad. Sci.1081, 417–433 (2006).
  • Lin M, Rikihisa Y. Ehrlichia chaffeensis and Anaplasma phagocytophilum lack genes for lipid A biosynthesis and incorporate cholesterol for their survival. Infect. Immun.71(9), 5324–5331 (2003).
  • Zhu B, Nethery KA, Kuriakose JA, Wakeel A, Zhang X, McBride JW. Nuclear translocated Ehrlichia chaffeensis ankyrin protein interacts with the mid A-stretch of host promoter and intronic Alu elements. Infect. Immun.77(10), 4243–4255 (2009).
  • Popov VL, Yu XJ, Walker DH. The 120-kDa outer membrane protein of Ehrlichia chaffeensis: preferential expression on dense-core cells and gene expression in Escherichia coli associated with attachment and entry. Microb. Path.28, 71–80 (2000).

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