Immunization of heat-killed Klebsiella pneumoniae promotes strong mucosal Th17 responses and protects mice from live infection (59.4)

Abstract

Abstract Bacterial pneumonia is a leading cause of mortality and one major pathogen associated with this disease is Klebsiella pneumoniae (KP). Thus, a vaccine against KP is in great need especially for immunocompromised patients. Here we show that intranasal immunization of mice with heat-killed KP strongly induces IL-17 production in the lung. Using an Il17f reporter mouse, we were able to sort IL-17F positive cells after immunization by FACS. Further analysis reveals that these cells are conventional CD4+TCR-beta+ Th17 cells and they express Il17a, Il17f, Il22, Rora and Rorc. These Th17 cells are antigen specific as they proliferate and produce IL-17 upon re-stimulation with heat-killed KP but not heat-killed Escherichia coli or Staphylococcus aureus. These responses ultimately lead to the protection of immunized mice from live KP infection. This immunization strategy also confers protection in B cell-deficient (mu-MT) mice, demonstrating the vaccination can be antibody independent. We also show that other mucosal routes of vaccination such as intragastric immunization also reduces bacterial burden during pulmonary infection, suggesting that Th17 cells can be primed or recruited from other mucosal sites distal to the lung and oral vaccine can be effective in pulmonary infection. These data suggest that the Th17 pathway can be a target of pulmonary vaccine development through intranasal or intragastric immunization.