Regulation of inflammation during pseudomonas aeruginosa lung infection : a role of AIM2 and RCAN1

Abstract

<i>Pseudomonas aeruginosa</i> is an opportunistic bacterial pathogen that is an important cause of infection among immunocompromised individuals. <i>P. aeruginosa</i> chronically infects cystic fibrosis patients, leading to declined pulmonary function and increased morbidity and mortality. Host innate immune system employs a variety of pattern recognition receptors (PRRs) to detect the conserved molecular patterns on invading <i>P. aeruginosa</i>. In healthy individuals, activation of these PRRs triggers a complex of downstream signalling pathways that induce production of various proinflammatory cytokines and efficiently eliminates <i>P. aeruginosa</i> from the host. However, dysregulation of these signalling pathways increases the susceptibility of the host to bacterial infection. Herein we identify that AIM2 inflammasome, an intracellular dsDNA sensor, is functionally redundant in IL-1β production and caspase-1 activation during <i>P. aeruginosa</i> lung infection. Furthermore, we reveal regulator of calcineurin-1 as a novel negative regulator of the TLR-MyD88-dependent signalling pathway in a mouse model of acute pneumonia using <i>P. aeruginosa</i> lipopolysaccharide. These findings improve our understanding of the molecular mechanisms of host defense against <i>P. aeruginosa</i> in innate immunity.