Susceptibility to Burkholderia pseudomallei is associated with host immuneresponses involving tumor necrosis factor receptor-1 (TNFR1) and TNF receptor-2 (TNFR2)

Barnes, Jodie L., Williams, Natasha L., and Ketheesan, Natkunam (2008) Susceptibility to Burkholderia pseudomallei is associated with host immuneresponses involving tumor necrosis factor receptor-1 (TNFR1) and TNF receptor-2 (TNFR2). FEMS Immunology & Medical Microbiology, 52 (3). pp. 379-388.

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Abstract

Melioidosis is caused by the facultative intracellular bacterium, Burkholderia pseudomallei. Using C57BL/6 mice, we investigated the role of macrophages, TNF-α, TNF receptor-1 (TNFR1) and TNF receptor-2 (TNFR2) in host defense against B. pseudomallei using an experimental model of melioidosis. This study has demonstrated that in vivo depletion of macrophages renders C57BL/6 mice highly susceptible to intranasal infection with B. pseudomallei, with significant mortality occurring within 5 days of infection. Using knockout mice, we have also shown that TNF-α and both TNFR1 and TNFR2 are required for optimal control of B. pseudomallei infection. Compared with control mice, increased bacterial loads were demonstrated in spleen and liver of knockout mice at day 2 postinfection, correlating with increased inflammatory infiltrates comprised predominantly of neutrophils and widespread necrosis. Following infection with B. pseudomallei, mortality rates of 85.7%, 70% and 91.7% were observed for mice deficient in TNF-α, TNFR1 and TNFR2, respectively. Comparison of survival, bacterial loads and histology indicate that macrophages, TNF-α, TNFR1 or TNFR2 play a role in controlling rapid dissemination of B. pseudomallei.

Item ID: 10229
Item Type: Article (Refereed Research - C1)
Keywords: melioidosis; Burkholderia pseudomallei; TNF-alpha; TNF receptors; C57BL/6
ISSN: 1574-695X
Date Deposited: 29 Apr 2010 01:49
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110801 Medical Bacteriology @ 30%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 30%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 40%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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