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Laboratory for Infection and Immunity, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
We investigated the role of NKT cells in immunity to Chlamydia pneumoniae and Chlamydia muridarum infections using a combination of knockout mice and specific cellular activation approaches. The NKT-deficient mice showed exacerbated susceptibility to C. pneumoniae infection, but more resistance to C. muridarum infection. Activation of NKT reduced C. pneumoniae in vivo growth, but enhanced C. muridarum infection. Cellular analysis of invariant NKT cells revealed distinct cytokine patterns following C. pneumoniae and C. muridarum infections, i.e., predominant IFN-
in the former, while predominant IL-4 in the latter. The cytokine patterns of CD4+ and CD8+ T cells matched those of NKT cells. Our data provide in vivo evidence for a functionally diverse role of NKT cells in immune response to two intracellular bacterial pathogens. These results suggest that distinct NKT subsets are induced by even biologically closely related pathogens, thus leading to differential adaptive immune response and infection outcomes.
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1 This work was supported by operating grants from the Canadian Institutes for Health Research (CIHR) and the Manitoba Health Research Council. X.Y. is Canada Research Chair in Infection and Immunity. A.G.J. is a recipient of Postdoctoral Fellowship Award from the International Centre for Infectious Diseases/CIHR National Training Program. L.B. is a recipient of a CIHR Doctoral Studentship and a trainee of the CIHR National Training Program in Allergy/Asthma.
2 Address correspondence and reprint requests to Dr. Xi Yang, Laboratory for Infection and Immunity, Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Room 523, BMSB, 730 William Avenue, Winnipeg, Manitoba R3E 0W3, Canada. E-mail address: yangxi{at}cc.umanitoba.ca
3 Abbreviations used in this paper: iNKT, invariant NKT;
-GalCer,
-galactosylceramide; MoPn, mouse pneumonitis; KO, knockout; IFU, inclusion-forming unit; EB, elementary body; D-PBS, Dulbeccos PBS; p.i., postinfection; WT, wild type.
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