Open AccessSequential Analysis of Anaplasma phagocytophilum msp2 Transcription in Murine and Equine Models of Human Granulocytic Anaplasmosis
Author(s) -
Diana G. Scorpio,
Christian M. Leutenegger,
Jeannine Berger,
Nicole Barat,
John E. Madigan,
J. Stephen Dumler
Publication year - 2008
Publication title -
clinical and vaccine immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.649
H-Index - 77
eISSN - 1556-6811
pISSN - 1556-679X
DOI - 10.1128/cvi.00417-07
Subject(s) - anaplasma phagocytophilum , biology , anaplasmosis , virology , immunology , antibody , seroconversion , borrelia burgdorferi , tick
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 inAnaplasma marginale , we hypothesized a similar event inA. phagocytophilum in vivo, with specific Msp2 expression triggering immunopathologic injury or clinical manifestations of disease. We examinedmsp2 transcripts in 11 B6 mice and 6 horses inoculated with low- or high-passageA. phagocytophilum Webster strain. Blood was sequentially obtained through 3 weeks postinfection formsp2 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 ofmsp2 transcripts, and all 22msp2 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, wheremsp2 diversity did not explain differences in hepatic histopathology, but differ from the paradigm of low-passageA. phagocytophilum causing more significant clinical illness. Alteration in transcription ofmsp2 has no bearing on clinical disease in horses, suggesting the existence of a separate proinflammatory component differentially expressed with changing in vitro passage.