An unconventional T cell population is critical for protection from repeat pulmonary infection with Klebsiella pneumoniae

Abstract

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.