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Infection and Immunity, July 2007, p. 3245-3255, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.01767-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

T Cells Are Essential for Bacterial Clearance, and Gamma Interferon, Tumor Necrosis Factor Alpha, and B Cells Are Crucial for Disease Development in Coxiella burnetii Infection in Mice{triangledown}

Masako Andoh,1 Guoquan Zhang,1 Kasi E. Russell-Lodrigue,1 Heather R. Shive,2 Brad R. Weeks,2 and James E. Samuel1*

Department of Microbial and Molecular Pathogenesis, Texas A&M University Health Science Center,1 Pathobiology Department, College of Veterinary Medicine, Texas A&M University, College Station, Texas2

Received 6 November 2006/ Returned for modification 14 December 2006/ Accepted 29 March 2007

Coxiella burnetii, the etiological agent of Q fever, has two phase variants. Phase I has a complete lipopolysaccharide (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 roles of immune components in animals infected with Nine Mile phase I (NM I) or Nine Mile phase II (NM II) bacteria. Immunodeficient mice, including SCID mice (deficient in T and B cells), SCIDbg mice (deficient in T, B, and NK cells), nude mice (deficient in T cells), muMT mice (deficient in B cells), bg mice (deficient in NK cells), mice deficient in tumor necrosis factor alpha (TNF-{alpha}–/– mice), and mice deficient in gamma interferon (IFN-{gamma}–/– mice), were compared for their responses 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-deficient 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.


* Corresponding author. Mailing address: Department of Microbial and Molecular Pathogenesis, Texas A&M Health Science Center, 407 Reynolds Bldg., College Station, TX 77843-1114. Phone: (979) 862-1684. Fax: (979) 845-3479. E-mail: jsamuel{at}tamhsc.edu

{triangledown} Published ahead of print on 16 April 2007.

Editor: R. P. Morrison


Infection and Immunity, July 2007, p. 3245-3255, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.01767-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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