Lymphotoxin-alpha plays only a minor role in host resistance to respiratory infection with virulent type A Francisella tularensis in mice.

This study examined the role of lymphotoxin (LT)-alpha in host defense against airborne infection with Francisella tularensis, a gram-negative facultative intracellular bacterium and the causative agent of tularemia. Following a low-dose aerosol infection with the highly virulent type A strain of F. tularensis, mice deficient in LT alpha (LT alpha-/-) consistently harbored approximately 10-fold fewer bacteria in their spleens at day 2 and 10-fold more bacteria in their lungs at day 4 than LT alpha+/+ mice. However, the mortality and median time to death were indistinguishable between the two mouse strains. In addition, the inflammatory responses to the infection, as reflected by the cytokine levels and leukocyte influx in the bronchoalveolar lavage fluid and histopathological analysis, were generally similar between LT alpha-/- and LT alpha+/+ mice. These data suggest that although LT alpha does not contribute significantly to the resistance and host responses of mice to airborne type A F. tularensis infection, it does play a subtle role in the multiplication/dissemination of F. tularensis. Copyright (C) 2008 Deng Zhang et al.