Klebsiella pneumoniae represents a growing clinical threat, given its rapid development of antibiotic resistance, necessitating new therapeutic strategies. Existing live-infection models feature high mortality rates, limiting their utility in the study of natural adaptive immune response to this pathogen. We developed a preclinical model of pneumonia with low overall mortality, in which previously exposed mice are protected from subsequent respiratory tract challenge with K. pneumoniae. Histologic analyses of infected murine lungs demonstrate lymphocytic aggregates surrounding vasculature and larger airways. Initial exposure in RAG1 knockout mice (lacking functional B and T cells) failed to confer protection against subsequent K. pneumoniae challenge. While administration of isolated K. pneumoniae capsule was sufficient to provide protection, we also found that initial inoculation with K. pneumoniae mutants lacking capsule (Δcps), O-antigen (ΔwecA) or both conferred protection from subsequent wild-type infection and elicited K. pneumoniae-specific antibody responses, indicating that noncapsular antigens may also elicit protective immunity. Experiments in this model will inform future development of multivalent vaccines to prevent invasive K. pneumoniae infections.

Klebsiella pneumoniae is a Gram-negative, opportunistic pathogen that commonly causes nosocomial pneumonia, urinary tract infection, and septicemia. Our recent work utilizing a murine model of respiratory tract infection with classical K. pneumoniae demonstrated leukocyte aggregates in the lungs of mice at 28 days postinfection.

Infections with classical strains of the Gram-negative bacterium Klebsiella pneumoniae pose a significant clinical challenge due to rising antibiotic resistance. We previously established a lung inoculation plus challenge model using live, classical K. pneumoniae in order to study host protection. Here, we employ this model to dissect adaptive immune responses to this critical pathogen. First, we performed convalescent serum transfers from inoculated mice to naïve recipients and found that classical K. pneumoniae infection outcomes, unlike hypervirulent K. pneumoniae infection outcomes, were not improved. This suggests that circulating antibody responses alone are not sufficient to mediate protection against this classical strain. Hence, we evaluated the role of T cells in protection against classical K. pneumoniae reinfection and demonstrated that mice lacking T cells are unable to establish a protective response. However, mice individually deficient in either of the major T cell subsets, γδ or αβ (classical T cells), effectively mount a protective response, indicating either subset alone is sufficient to mediate protection. Sequestration of T cells in secondary lymphoid organs during the challenge infection did not ablate protection, indicating the circulating T cell pool is not required for the protective phenotype. Finally, we demonstrate that depletion of T cells during initial infection eliminates protection against challenge. Collectively, these experiments demonstrate the imperative contribution of T cells to protective immunity against classical K. pneumoniae and will guide further inquiries into host effector responses required to control this infection.

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