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

Author(s)

Codo, Ana Campos ^[1] ; Saraiva, Amanda Correia ^[1] ; dos Santos, Leonardo Lima ^[2] ; Visconde, Marina Francisco ^[3] ; Gales, Ana Cristina ^[3] ; Zamboni, Dario Simoes ^[2] ; Medeiros, Alexandra Ivo ^[1]

Affiliation

^[1] Sao Paulo State Univ, Sch Pharmaceut Sci, Dept Biol Sci, Araraquara, SP - Brazil

^[2] Univ Sao Paulo, Sch Med, Dept Cell & Mol Biol & Pathogen Bioagents, Ribeirao Preto, SP - Brazil

^[3] Univ Fed Sao Paulo, Dept Internal Med, Escola Paulista Med, Div Infect Dis, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: CELL DEATH & DISEASE; v. 9, DEC 5 2018.
• Web of Science Citations: 3

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-1 beta production and pyroptotic cell death in macrophages; by contrast, the A54970 strain induced high IL-10 production and low IL-1 beta 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. (AU)

• FAPESP's process: 13/18039-0 - Evaluation of the mechanisms of bacterial virulence and fitness of clinical isolates of Klebsiella pneumoniae subsp. pneumoniae producing KPC-2
• Grantee: Ana Cristina Gales
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/17611-7 - Effect of efferocytosis by dendritic cells on Th17 differentiation: role of Prostaglandin E2
• Grantee: Alexandra Ivo de Medeiros
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 17/19870-6 - Effect of phagocytosis of infected apoptotic cells during activation of M1/M2 Macrophages
• Grantee: Alexandra Ivo de Medeiros
• Support Opportunities: Regular Research Grants