Sequential analysis of Anaplasma phagocytophilum msp2 transcription in murine and equine models of human granulocytic anaplasmosis.
Anaplasma phagocytophilum causes human granulocytic anaplasmosis by inducing immunopathologic responses. Its immunodominant Msp2 protein is encoded by a family of >100 paralogs. Msp2 (msp2) expression modulates in the absence of immune pressure, and prolonged in vitro passage modulates in vivo virulence. Because programmed MSP2 expression occurs in Anaplasma marginale, we hypothesized a similar event in A. phagocytophilum in vivo, with specific Msp2 expression triggering immunopathologic injury or clinical manifestations of disease. We examined msp2 transcripts in 11 B6 mice and 6 horses inoculated with low- or high-passage A. phagocytophilum Webster strain. Blood was sequentially obtained through 3 weeks postinfection for msp2 reverse transcription-PCR. Horses were additionally assessed for clinical manifestations, seroconversion, complete blood count, blood chemistry, and cytokine gene transcription. In both species, there was no consistent emergence of msp2 transcripts, and all 22 msp2 variants were detected in both passage groups. Clinical severity was much higher for high-passage-infected than for low-passage-infected horses, preceded by higher levels of blood gamma interferon transcription on day 7. Antibody was first detected on day 7, and all horses seroconverted by day 22, with a trend toward lower antibody titers in low-passage-infected animals. Leukocyte and platelet counts were similar between experimental groups except on day 13, when low-passage-infected animals had more profound thrombocytopenia. These findings corroborate studies with mice, where msp2 diversity did not explain differences in hepatic histopathology, but differ from the paradigm of low-passage A. phagocytophilum causing more significant clinical illness. Alteration in transcription of msp2 has no bearing on clinical disease in horses, suggesting the existence of a separate proinflammatory component differentially expressed with changing in vitro passage.
Scorpio
Diana G
DG
Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. dscorpio@jhmi.edu
Leutenegger
Christian
C
Berger
Jeannine
J
Barat
Nicole
N
Madigan
John E
JE
Dumler
J Stephen
JS
D041081:Anaplasma phagocytophilum / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D016873:Ehrlichiosis / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D018922:HL-60 Cells; D006734:Horse Diseases / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D006736:Horses; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012692:Serial Passage; D014158:Transcription, Genetic
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; C488283:msp2 protein, Anaplasma phagocytophilum