2-Microglobulin-Dependent Bacterial Clearance and Survival during Murine Klebsiella pneumoniae Bacteremia

Klebsiella pneumoniae is a leading cause of both community-acquired and nosocomial gram-negative bacterial pneumonia. A significant clinical complication of Klebsiella pulmonary infections is peripheral blood dissemination, resulting in a systemic infection concurrent with the localized pulmonary infection. We report here on the critical importance of 2-microglobulin expression during murine K. pneumoniae bacteremia. 2-Microglobulin knockout mice displayed significantly increased mortality upon intravenous inoculation that correlated with increased bacterial burden in the blood, liver, and spleen. As 2-microglobulin knockout mice lack both CD8 T cells and invariant NK T cells, mouse models specifically deficient in either cell population were examined to see if this would account for the increased mortality noted in 2-microglobulin knockout mice. Surprisingly, neither CD8 T-cell-deficient (TAP-1 knockout; in vivo anti-CD8 antibody treatment) nor invariant NK (iNK) T-cell-deficient (CD1d knockout, J 281 knockout) mice were more susceptible to K. pneumoniae bacteremia. Combined, these studies clearly indicate the importance of a 2-microglobulin-dependent but CD8 T-celland iNK T-cell-independent mechanism critical for survival during K. pneumoniae bacteremia.