Beta2-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 beta(2)-microglobulin expression during murine K. pneumoniae bacteremia. Beta(2)-microglobulin knockout mice displayed significantly increased mortality upon intravenous inoculation that correlated with increased bacterial burden in the blood, liver, and spleen. As beta(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 beta(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 alpha281 knockout) mice were more susceptible to K. pneumoniae bacteremia. Combined, these studies clearly indicate the importance of a beta(2)-microglobulin-dependent but CD8 T-cell- and iNK T-cell-independent mechanism critical for survival during K. pneumoniae bacteremia.
Cogen
Anna L
AL
Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0642, USA.
Moore
Thomas A
TA
D000818:Animals; D016470:Bacteremia / Q000276:immunology* / Q000382:microbiology*; D001769:Blood / Q000382:microbiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015169:Colony Count, Microbial; D007694:Killer Cells, Natural / Q000276:immunology; D007711:Klebsiella pneumoniae / Q000276:immunology*; D008099:Liver / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000382:microbiology; D016019:Survival Analysis; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000276:immunology*
D001613:beta 2-Microglobulin