A critical role for neutrophils in resistance to experimental infection with Burkholderia pseudomallei


Easton, A; Haque, A; Chu, K; Lukaszewski, R; Bancroft, GJ; (2007) A critical role for neutrophils in resistance to experimental infection with Burkholderia pseudomallei. The Journal of infectious diseases, 195 (1). pp. 99-107. ISSN 0022-1899 DOI: https://doi.org/10.1086/509810

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Abstract

Inhalation is an important route of infection with Burkholderia pseudomallei, the causative agent of melioidosis. In resistant C57BL/6 mice, activated neutrophils are rapidly recruited to the lungs after intranasal B. pseudomallei infection. Prevention of this response by use of the anti-Gr-1(+) cell-depleting monoclonal antibody RB6-8C5 severely exacerbated disease, resulting in an acute lethal infection associated with a 1000-fold increase in lung bacterial loads within 4 days. C57BL/6 interferon (IFN)-gamma(-/-) mice were also acutely susceptible to pulmonary B. pseudomallei infection, dying within 3 days of challenge; this suggests that IFN-gamma is essential for control in the lungs and precedes the protective role of neutrophils in resistance. In neutrophil-depleted mice, lung concentrations of tumor necrosis factor (TNF)-alpha, IFN-gamma, and interleukin-6 were decreased by up to 98%. Natural killer cells were the principle source of IFN-gamma, and monocytes were the principle source of TNF-alpha, suggesting that neutrophils play an important indirect role in the generation of the early cytokine environment in the lungs.

Item Type: Article
Keywords: HUMAN POLYMORPHONUCLEAR LEUKOCYTES, C57BL/6 MICE, MURINE MODEL, PSEUDOMONAS-PSEUDOMALLEI, HUMAN MELIOIDOSIS, MYCOBACTERIUM-TUBERCULOSIS, LISTERIA-MONOCYTOGENES, MONOCLONAL-ANTIBODY, BACTERIAL CLEARANCE, GAMMA-INTERFERON
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
PubMed ID: 17152013
Web of Science ID: 242480600012
URI: http://researchonline.lshtm.ac.uk/id/eprint/10508

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