Differential innate immune cell activation and proinflammatory response in Anaplasma phagocytophilum infection

Kyoung Seong Choi, Tonya Webb, Mathias Oelke, Diana G. Scorpio, J. Stephen Dumler

Research output: Contribution to journalArticle

Abstract

Human granulocytic anaplasmosis (HGA) is caused by the obligate intracellular bacterium Anaplasma phagocytophilum. The critical role of gamma interferon (IFN-γ) 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-γ 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.

Original languageEnglish (US)
Pages (from-to)3124-3130
Number of pages7
JournalInfection and Immunity
Volume75
Issue number6
DOIs
StatePublished - Jun 2007

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Anaplasma phagocytophilum
Infection
Natural Killer T-Cells
Anaplasmosis
Liver
Bacterial Load
Cellular Structures
Natural Killer Cells
Interferons
Interferon-gamma
Lymphocytes
Apoptosis
Inflammation
Bacteria
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

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Differential innate immune cell activation and proinflammatory response in Anaplasma phagocytophilum infection. / Choi, Kyoung Seong; Webb, Tonya; Oelke, Mathias; Scorpio, Diana G.; Dumler, J. Stephen.

In: Infection and Immunity, Vol. 75, No. 6, 06.2007, p. 3124-3130.

Research output: Contribution to journalArticle

Choi, Kyoung Seong ; Webb, Tonya ; Oelke, Mathias ; Scorpio, Diana G. ; Dumler, J. Stephen. / Differential innate immune cell activation and proinflammatory response in Anaplasma phagocytophilum infection. In: Infection and Immunity. 2007 ; Vol. 75, No. 6. pp. 3124-3130.
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