Inhibition of inflammasome activation by a clinical strain of Klebsiella pneumoniae impairs efferocytosis and leads to bacterial dissemination.

ABSTRACT

Klebsiella pneumoniae is a Gram-negative bacterium responsible for severe cases of nosocomial pneumonia. During the infectious process, both neutrophils and monocytes migrate to the site of infection, where they carry out their effector functions and can be affected by different patterns of cell death. Our data show that clinical strains of K. pneumoniae have dissimilar mechanisms for surviving within macrophages; these mechanisms include modulation of microbicidal mediators and cell death. The A28006 strain induced high IL-1ß production and pyroptotic cell death in macrophages; by contrast, the A54970 strain induced high IL-10 production and low IL-1ß production by macrophages. Pyroptotic cell death induced by the A28006 strain leads to a significant increase in bacterial sensitivity to hydrogen peroxide, and efferocytosis of the pyroptotic cells results in efficient bacterial clearance both in vitro and in vivo. In addition, the A54970 strain was able to inhibit inflammasome activation and pyroptotic cell death by inducing IL-10 production. Here, for the first time, we present a K. pneumoniae strain able to inhibit inflammasome activation, leading to bacterial survival and dissemination in the host. The understanding of possible escape mechanisms is essential in the search for alternative treatments against multidrug-resistant bacteria.