This Article Full Text Full Text (PDF) Other Versions of this Article: CVI.00417-07v1 15/3/418    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Scorpio, D. G. Articles by Dumler, J. S. PubMed PubMed Citation Articles by Scorpio, D. G. Articles by Dumler, J. S.

Sequential Analysis of Anaplasma phagocytophilum msp2 Transcription in Murine and Equine Models of Human Granulocytic Anaplasmosis

Diana G. Scorpio,^1* Christian Leutenegger,^3, Jeannine Berger,³ Nicole Barat,² John E. Madigan,³ and J. Stephen Dumler²

Department of Molecular and Comparative Pathobiology,¹ Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland,² Department of Epidemiology and Medicine, School of Veterinary Medicine, University of California, Davis, California³

Received 15 October 2007/ Returned for modification 20 November 2007/ Accepted 8 December 2007

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.

Published ahead of print on 19 December 2007.

Present address: IDEXX Reference Laboratories, West Sacramento, CA.