Klebsiella pneumoniae is a worrisome nosocomial pathogen given the widespread emergence of antibiotic resistant strains. Little is known about the host immune response to K. pneumoniae; however, it has recently been shown that aggregates of lymphoid cells can be found in murine lungs 4 weeks after surviving K. pneumoniae pulmonary infection. Others have characterized pulmonary collections of lymphoid cells in response to other pathogens and coined them induced bronchus-associated lymphoid tissue (iBALT). iBALT is believed to assist in protection against re-infection. In our nonlethal model of K. pneumoniae, mice that survive the primary infection and exhibit these structures are indeed protected from K. pneumoniae challenge. To further characterize the development and organization of these structures, pulmonary immune cell populations were analyzed post-infection by flow cytometry, histology, and immunofluorescence. As expected, pulmonary neutrophil populations increase over the first 10 days post-infection. T cells appear to rapidly expand between 7 and 10 days post-infection and both CD4+ and γδ T cell subsets make up the majority of this population. Immunofluorescent imaging of lymphoid aggregates demonstrate that CD4+ and γδ T cells are found within these structures at early time-points. Experiments using TCRβδ−/− mice lacking T cells reveals the absence of lymphoid aggregates 28 days post-infection, suggesting that T cells are essential in the initial formation and development of these structures.
Due to emerging antibiotic resistance, the nosocomial pathogen Klebsiella pneumoniae is an increasing public health threat. The extent to which survivors are protected against re-infection, or potential correlates of such protection, are poorly understood. We have explored the immunological mechanisms required for protection against K. pneumoniae re-infection using a nonlethal murine model of pulmonary K. pneumoniae challenge. Mice that survive K. pneumoniae TOP52 infection are protected from subsequent re-infection by an adaptive immune response. Genetically modified mice lacking mature lymphocytes or mature T cells were equally susceptible to primary and secondary infection, suggesting that T cells are required for protection. Intriguingly, neither CD4+ nor CD8+ T cells were absolutely required for either the establishment or execution of a protective memory response as depletion of CD4+ and/or CD8+ T cells during either primary or secondary infection did not impair protection against re-infection. However, we observe an expansion of γδ T cells following primary exposure to K. pneumoniae and a profound amplification of this population following secondary infection. Experiments using genetically modified mice deficient in γδ T cells or intact mice treated with γδ T cell depleting antibodies suggest that this T cell subpopulation is important for protection against re-infection. Thus, we hypothesize that K. pneumoniae exposure drives the development of a resident memory-like population of γδ T cells that are maintained in the lung and contribute to the efficient control of secondary K. pneumoniae infection.
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