A critical role for neutrophils in resistance to experimental infection with Burkholderia pseudomallei.
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.
Easton
Anna
A
London School of Hygiene and Tropical Medicine, London, WC1E 7HT, United Kingdom.
Haque
Ashraful
A
Chu
Karen
K
Lukaszewski
Roman
R
Bancroft
Gregory J
GJ
D000818:Animals; D016957:Burkholderia pseudomallei / Q000276:immunology* / Q000472:pathogenicity*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000276:immunology*; D008554:Melioidosis / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*
D016207:Cytokines