Role of Neutrophils and NADPH Phagocyte Oxidase in Host Defense Against Respiratory Infection With Virulent Francisella Tularensis in Mice

Microbes Infect. 2011 May;13(5):447-56. doi: 10.1016/j.micinf.2011.01.010. Epub 2011 Jan 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / immunology
  • Female
  • Francisella tularensis / immunology
  • Francisella tularensis / pathogenicity*
  • Humans
  • Immunity, Innate
  • Lung / immunology
  • Lung / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NADPH Oxidases / deficiency
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism*
  • Neutrophil Infiltration
  • Neutrophils / immunology*
  • Phagocytes / enzymology*
  • Respiratory Burst
  • Respiratory Tract Infections / immunology*
  • Respiratory Tract Infections / microbiology
  • Tularemia / immunology*
  • Tularemia / microbiology

Substances

  • NADPH Oxidases