Msp2 variation in Anaplasma phagocytophilum in vivo does not stimulate T cell immune responses or interferon-gamma production.
Msp2 is Anaplasma phagocytophilum's immunodominant protein. Antigenic variability with msp2 gene conversion may drive differential immunopathology with infection by bacteria of different in vitro passage intervals. We examined msp2 transcript variation and its relationship to histopathology, T-cell and antibody responses in mice infected with differentially passaged A. phagocytophilum. Hepatic inflammation peaked on day 2-4 with low passage bacteria and on day 4-7 with high passage bacteria infection. Nineteen msp2 variant transcripts were identified. The low and high passage inocula shared four, but differed in one and two msp2 transcript variants, respectively. After infection, three and two msp2 variants were only identified in low or high passage infected mice. However, per mouse, msp2 variant profiles were unique with no evident expression program. In low and high passage bacteria-infected mice, splenocytes proliferated to whole A. phagocytophilum at day 7-10, diminishing thereafter. Weak mitogenic responses to whole bacteria were detected in mock and infected mice at d0 and sporadically thereafter. Essentially no lymphoproliferation or IFN-gamma production resulted from stimulation by six Msp2 hypervariable region proteins, although antibodies were detected to all, including cross-reactions. Differential A. phagocytophilum Msp2 expression is unrelated to T-cell response and unlikely to induce the cellular immunopathology underlying disease manifestations.
Choi
Kyoung-Seong
KS
Division of Medical Microbiology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Scorpio
Diana G
DG
Barat
Nicole C
NC
Stephen Dumler
J
J
D000595:Amino Acid Sequence; D041081:Anaplasma phagocytophilum / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000940:Antigenic Variation; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D016873:Ehrlichiosis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D006651:Histocytochemistry; D007371:Interferon-gamma / Q000096:biosynthesis*; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012329:RNA, Bacterial / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017422:Sequence Analysis, DNA; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D012329:RNA, Bacterial; D012333:RNA, Messenger; C488283:msp2 protein, Anaplasma phagocytophilum; D007371:Interferon-gamma