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Infect. Immun. doi:10.1128/IAI.01767-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

T cells are essential for bacterial clearance and IFN{gamma}, TNF{alpha}, and B cells are crucial for disease development in Coxiella burnetii infection in mice

Masako Andoh, Guoquan Zhang, Kasi E. Russell-Lodrigue, Heather R. Shive, Brad R. Weeks, and James E. Samuel*

Department of Microbial and Molecular Pathogenesis, Texas A&M University Health Science Center, Pathobiology Department, College of Veterinary Medicine, Texas A&M University, TX, USA

* To whom correspondence should be addressed. Email: jsamuel{at}tamhsc.edu.


   Abstract

Coxiella burnetii, the etiological agent of Q fever, has two phase variants. Phase I has a complete LPS, is highly virulent, and causes Q fever in humans and pathology in experimental animals. Phase II lacks an LPS O-side chain, is avirulent, and does not grow well in immunocompetent animals. To understand the pathogenicity of Q fever, we investigated the role of immune components in animals infected with Nine Mile phase I (NM I) or phase II (NM II). Immunodeficient mice, including SCID ({Delta} T and B cell), SCIDbg ({Delta} T, B and NK cell), nude ({Delta} T cell), muMT ({Delta} B cell), bg ({Delta} NK cell), TNF{alpha}-/-, and IFN{gamma}-/-, were compared for their response to infection. SCID, SCIDbg, nude and IFN{gamma}-/- mice showed high susceptibility to NM I, and TNF{alpha}-/- mice showed modest susceptibility. Disease caused by NM I in SCID, SCIDbg and nude mice progressed slowly, while disease in IFN{gamma}-/- and TNF{alpha}-/- mice advanced rapidly. B and NK cell deficiencies did not enhance clinical disease development or alter bacterial clearance but did increase the severity of histopathological changes, particularly in the absence of B cells. Mice infected with NM II showed no apparent clinical disease, but T cell deficiency mice had histopathological changes. These results suggest that T cells are critical for clearance of C. burnetii, either NM I or NM II, that IFN{gamma} and TNF{alpha} are essential for the early control of infection, and that B cells are important for the prevention of tissue damage.




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