Early activation of NK cells after lung infection with the intracellular bacterium, Francisella tularensis LVS

Francisella tularensis is a gram-negative intracellular bacterium that has been classified as a Category A biothreat because of its ability to induce deadly pneumonic tularemia when inhaled. In the present Study, an experimental model of F tularensis LVS intranasal infection was used to study the immune cells involved in cytokine secretion in the lungs after infection. Dramatic increases in the numbers of cells secreting IFN-gamma were observed 72 h after intranasal infection of BALB/c and C57BL/6 mice with Sublethal (1000 CFU) or lethal (10,000 CFU) doses of F. tularensis LVS and the cells primarily responsible for this IFN-gamma expression were identified as CD11b(+) DX5(+) NK cells. The findings were further confirmed in C57BL/6 mice showing that cells responsible for IFN-gamma secretion in the lungs were CD11b(+) DX5(+) NK1.1(+). NK cell depletion studies showed a decrease in the percentage of IFN-gamma secreting cells, due not only to a diminished proportion of IFN-gamma secreting NK cells, but also to a reduced percentage of T cells secreting IFN-gamma. The results indicate that IFN-gamma is secreted in response to respiratory infection with F tularensis LVS, and that NK cells are the early responders responsible for IFN-gamma secretion, (c) 2005 Elsevier Inc. All rights reserved.