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* Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada;
Department of Immunology, Tianjin Medical University, Tianjin, China; and
Department of Molecular Cell Biology, Vrije Universiteit, Amsterdam, The Netherlands
Type I IFNs (IFNIs) have pleiotropic functions in regulating host innate and adaptive immune responses to pathogens. To elucidate the role of IFNIs in host resistance to chlamydial infection in vivo, we compared IFN-
/β receptor knockout (IFNAR–/–) and wild-type control mice in susceptibility to Chlamydia trachomatis mouse pneumonitis (Chlamydia muridarum) lung infection. We found that the IFNAR–/– mice were significantly more resistant to C. muridarum infection showing less bacterial burden and bodyweight loss, and milder pathological changes. However, IFN-
response, which is believed to be critical in host defense against chlamydial infection, was similar between the wild-type and IFNAR–/– mice. More importantly, TUNEL analysis showed less macrophage apoptosis in IFNAR–/– mice, which was consistent with lower expressions of IFNI-induced apoptotic factors, TRAIL, Daxx, and PKR. Furthermore, depletion of lung macrophages with dichloromethylene diphosphonate-liposome significantly increased the susceptibility of the IFNAR–/– mice to C. muridarum, confirming the importance of macrophages. Overall, the data indicate that IFNIs play a promoting role in C. muridarum lung infection, largely through increase of local macrophage apoptosis.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants (to X.Y.) from Canadian Institutes of Health Research, Manitoba Health Research Council, and Manitoba Institute of Child Health. H.Q. and A.G.J. are trainees in the Canadian Institutes of Health Research/International Centre for Infectious Diseases National Training Program in Infectious Diseases. H.Q. was also a holder of Manitoba Health Research Council Studentship and Health Sciences Foundation of Winnipeg Studentship. X.H. and L.J. were trainees in the Canadian Institutes of Health Research National Training Program in Allergy/asthma. X.Y. is Canada Research Chair in Infection and Immunity.
2 Address correspondence and reprint requests to Dr. Xi Yang, Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Room 523, 730 William Avenue, Winnipeg, Manitoba, Canada R3E 0W3. E-mail address: yangxi{at}cc.umanitoba.ca
3 Abbreviations used in this paper: IFNI, IFN type I; IFU, inclusion forming unit; IFNAR–/–, IFN-/β receptor knockout; WT, wild type; KO, knockout; BAL, bronchioalveolar lavage; DC, dendritic cell; CL2MDP, dichloromethylene diphosphonate; p.i., postinfection.
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