TY - JOUR
T1 - Differential innate immune cell activation and proinflammatory response in Anaplasma phagocytophilum infection
AU - Choi, Kyoung Seong
AU - Webb, Tonya
AU - Oelke, Mathias
AU - Scorpio, Diana G.
AU - Dumler, J. Stephen
PY - 2007/6
Y1 - 2007/6
N2 - 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.
AB - 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.
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U2 - 10.1128/IAI.00098-07
DO - 10.1128/IAI.00098-07
M3 - Article
C2 - 17403880
AN - SCOPUS:34249903322
SN - 0019-9567
VL - 75
SP - 3124
EP - 3130
JO - Infection and immunity
JF - Infection and immunity
IS - 6
ER -