title: A critical role for neutrophils in resistance to experimental infection with Burkholderia pseudomallei.
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.
authors.affiliation: London School of Hygiene and Tropical Medicine, London, WC1E 7HT, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Easton
authors.forename: Ashraful
authors.initials: A
authors.lastname: Haque
authors.forename: Karen
authors.initials: K
authors.lastname: Chu
authors.forename: Roman
authors.initials: R
authors.lastname: Lukaszewski
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bancroft
mesh_terms: 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*
chemical_list: D016207:Cytokines