Classical and γδ T cells are each independently sufficient to establish protection against a classical strain of Klebsiella pneumoniae

Abstract

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.

Capsular polysaccharide inhibits vaccine-induced O-antigen antibody binding and function across both classical and hypervirulent K2:O1 strains ofKlebsiella pneumoniae

“…Further, as capsule is required for lung virulence ( 42, 43 ) it is not feasible to do a challenge study to test vaccine efficacy with the capsule mutants in lieu of a lower inoculum or immunocompromised model. Fifth, we have recently shown that some c Kp infections may not rely solely on antibody responses to fight infection, which could offer an additional explanation for the survival differences we observed in hv Kp and c Kp survival models ( 44 ). Finally, the means by which the presence of capsule renders O-antibodies less effective is not mechanistically defined here.…”

Capsular polysaccharide inhibits vaccine-induced O-antigen antibody binding and function across both classical and hypervirulent K2:O1 strains of Klebsiella pneumoniae

“…Further, as capsule is required for lung virulence [ 46 , 47 ] it is not feasible to do a challenge study to test vaccine efficacy with the capsule mutants in lieu of a lower inoculum or immunocompromised model. Fifth, we have recently shown that some c Kp infections may not rely solely on antibody responses to fight infection, which could offer an additional explanation for the survival differences we observed in hv Kp and c Kp survival models [ 48 ]. Finally, the means by which the presence of capsule renders O-antibodies less effective is not mechanistically defined here.…”

Host defense against the infection of Klebsiella pneumoniae: New strategy to kill the bacterium in the era of antibiotics?

“…Recently, Mackel et al evaluated the role of T cells in protection against classical K. pneumoniae reinfection and demonstrated that mice lacking T cells were unable to establish a protective response. However, mice individually deficient in either of the major T cell subsets, gd or ab (classical T cells), effectively mounted a protective response, indicating either subset alone was sufficient to mediate protection against the reinfection of K. pneumoniae (Mackel et al, 2022) (Figure 5). The researches above demonstrate the imperative contribution of innate T cells to protective immunity against classical K. pneumoniae and will guide further inquiries into host effector responses required to control K. pneumoniae infection.…”