title: Differential innate immune cell activation and proinflammatory response in Anaplasma phagocytophilum infection.
abstract: Human granulocytic anaplasmosis (HGA) is caused by the obligate intracellular bacterium Anaplasma phagocytophilum. The critical role of gamma interferon (IFN-gamma) for induction of severe inflammatory histopathology, even in the absence of a significant bacterial load, was previously demonstrated in a murine model of HGA. We hypothesized that NK, NKT, and possibly CD8(+) cytotoxic T cells participate in the development of histopathologic lesions with A. phagocytophilum infection. Mice were mock infected or infected with low- or high-passage A. phagocytophilum and assayed for hepatic histopathology and splenocyte immunophenotype during the first 21 days after infection. Compared to high-passage A. phagocytophilum-infected mice, low-passage A. phagocytophilum-infected mice had more severe hepatic lesions and increased apoptosis. The hepatic histopathology severity in low-passage A. phagocytophilum-infected mice peaked on day 2 at the time of peak plasma IFN-gamma levels and gradually decreased through day 21. Low-passage A. phagocytophilum-infected mice also showed significantly increased levels of lymphocyte NK1.1/FasL expression on days 4 to 7 corresponding to early, severe hepatic inflammation, whereas the levels of NKT cells were substantially lower on day 4, suggesting that there was NKT cell involvement. This result supports the concept that NK1.1(+) cells, including NK and NKT cells, are major components in the early pathogenesis of A. phagocytophilum infection.
authors.affiliation: Division of Medical Microbiology, Department of Pathology, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 624, Baltimore, MD 21205, USA.
authors.forename: Kyoung-Seong
authors.initials: KS
authors.lastname: Choi
authors.forename: Tonya
authors.initials: T
authors.lastname: Webb
authors.forename: Mathias
authors.initials: M
authors.lastname: Oelke
authors.forename: Diana G
authors.initials: DG
authors.lastname: Scorpio
authors.forename: J Stephen
authors.initials: JS
authors.lastname: Dumler
mesh_terms: D041081:Anaplasma phagocytophilum / Q000276:immunology* / Q000472:pathogenicity; D000712:Anaplasmosis / Q000276:immunology*; D000818:Animals; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL