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Membrane vesicles from Pseudomonas aeruginosa activate the noncanonical inflammasome through caspase‐5 in human monocytes
Author(s) -
Bitto Natalie J,
Baker Paul J,
Dowling Jennifer K,
WrayMcCann Georgie,
De Paoli Amanda,
Tran Le Son,
Leung Pak Ling,
Stacey Katryn J,
Mansell Ashley,
Masters Seth L,
Ferrero Richard L
Publication year - 2018
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12190
Subject(s) - inflammasome , pyroptosis , caspase 1 , innate immune system , microbiology and biotechnology , pseudomonas aeruginosa , biology , lipopolysaccharide , aim2 , secretion , caspase , immune system , inflammation , apoptosis , immunology , bacteria , programmed cell death , biochemistry , genetics
Outer membrane vesicles ( OMV s) are constitutively produced by Gram‐negative bacteria both in vivo and in vitro . These lipid‐bound structures carry a range of immunogenic components derived from the parent cell, which are transported into host target cells and activate the innate immune system. Recent advances in the field have shed light on some of the multifaceted roles of OMV s in host–pathogen interactions. In this study, we investigated the ability of OMV s from two clinically important pathogens, Pseudomonas aeruginosa and Helicobacter pylori , to activate canonical and noncanonical inflammasomes. P. aeruginosa OMV s induced inflammasome activation in mouse macrophages, as evidenced by “speck” formation, as well as the cleavage and secretion of interleukin‐1β and caspase‐1. These responses were independent of AIM 2 and NLRC 4 canonical inflammasomes, but dependent on the noncanonical caspase‐11 pathway. Moreover, P. aeruginosa OMV s alone were able to activate the inflammasome in a TLR ‐dependent manner, without requiring an exogenous priming signal. In contrast, H. pylori OMV s were not able to induce inflammasome activation in macrophages. Using CRISPR /Cas9 knockout THP ‐1 cells lacking the human caspase‐11 homologs, caspase‐4 and ‐5,we demonstrated that caspase‐5 but not caspase‐4 is required for inflammasome activation by P. aeruginosa OMV s in human monocytes. In contrast, free P. aeruginosa lipopolysaccharide ( LPS ) transfected into cells induced inflammasome responses via caspase‐4. This suggests that caspase‐4 and caspase‐5 differentially recognize LPS depending on its physical form or route of delivery into the cell. These findings have relevance to Gram‐negative infections in humans and the use of OMV s as novel vaccines.