IL-15/IL-15Rα improves immune cell survival but does not reduce disease severity following pulmonary infection with the intracellular bacterium Francisella tularensis (56.27)

Abstract

Abstract The potent anti-apoptotic cytokine IL-15 regulates the development and function of a wide range of innate and adaptive immune cells. Treatment with IL-15 in combination with IL-15Rα prevents apoptosis and immunosuppression in mouse models of sepsis. Inhalation of Francisella tularensis results in an acute pneumonia that demonstrates many of the hallmarks of sepsis including bacteremia and hypercytokinemia. We and others have observed widespread cell death in the lung following infection with virulent F. tularensis strain Schu S4. The predominant cell populations depleted are lymphocytes and neutrophils. Cell numbers declined in Schu S4-infected mice despite high levels of chemokines in the lung and correlated with an increase in TUNEL-positive cells. This supports the conclusion that immune cell depletion was due to cell death, and not a lack of recruitment. To determine whether this cell depletion was contributing to Schu S4 pathogenesis, mice were treated with IL-15/IL-15Rα prior to infection. IL-15/IL-15Rα treatment significantly increased the number of viable lung cells in Schu S4-infected mice compared to mock-treated controls, however, no difference in bacterial burden or disease severity was observed. These data suggest that depletion of immune cells by F. tularensis does not contribute to the morbidity and mortality associated with pneumonic tularemia. Moreover, IL-15/IL-15Rα may not be generally applicable to treat sepsis of different etiologies.