title: Role of neutrophils and NADPH phagocyte oxidase in host defense against respiratory infection with virulent Francisella tularensis in mice.
abstract: Francisella tularensis subspecies (subsp.) tularensis is a CDC Category A biological warfare agent and inhalation of as few as 15 bacilli can initiate severe disease. Relatively little is known about the cellular and molecular mechanisms of host defense against respiratory infection with subsp. tularensis. In this study, we examined the role of neutrophils and NADPH phagocyte oxidase in host resistance to pulmonary infection in a mouse intranasal infection model. We found that despite neutrophil recruitment to the lungs and increased concentrations of neutrophil-chemotactic chemokines (KC, MIP-2 and RANTES) in the bronchoalveolar lavage fluid following intranasal inoculation of the pathogen, neither depletion of neutrophils nor enhancement of their recruitment into the lungs had any impact on bacterial burdens or survival rate/time. Nevertheless, mice deficient in NADPH phagocyte oxidase (gp91(phox⁻/⁻)) did exhibit higher tissue and blood bacterial burdens and succumbed to infection one day earlier than wild-type C57BL/6 mice. These results imply that although neutrophils are not a major effector cell in defense against subsp. tularensis infection, NADPH phagocyte oxidase does play a marginal role.
authors.affiliation: Institute for Biological Sciences, National Research Council Canada, 100 Sussex Drive, Ottawa, Ontario K1A0R6, Canada.
authors.forename: Rhonda
authors.initials: R
authors.lastname: KuoLee
authors.forename: Greg
authors.initials: G
authors.lastname: Harris
authors.forename: J Wayne
authors.initials: JW
authors.lastname: Conlan
authors.forename: Wangxue
authors.initials: W
authors.lastname: Chen
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D005260:Female; D005604:Francisella tularensis / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology*; D010586:Phagocytes / Q000201:enzymology*; D016897:Respiratory Burst; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000382:microbiology; D014406:Tularemia / Q000276:immunology* / Q000382:microbiology
chemical_list: D019255:NADPH Oxidases