| First Author | Cai S | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 11 | Pages | 5623-35 |
| PubMed ID | 22547706 | Mgi Jnum | J:188721 |
| Mgi Id | MGI:5441661 | Doi | 10.4049/jimmunol.1200195 |
| Citation | Cai S, et al. (2012) NLRC4 inflammasome-mediated production of IL-1beta modulates mucosal immunity in the lung against gram-negative bacterial infection. J Immunol 188(11):5623-35 |
| abstractText | Bacterial flagellin is critical to mediate NLRC4 inflammasome-dependent caspase-1 activation. However, Shigella flexneri, a nonflagellated bacterium, and a flagellin (fliC) knockout strain of Pseudomonas aeruginosa are known to activate NLRC4 in bone marrow-derived macrophages. Furthermore, the flagellin-deficient fliC strain of P. aeruginosa was used in a mouse model of peritonitis to show the requirement of NLRC4. In a model of pulmonary P. aeruginosa infection, flagellin was shown to be essential for the induction of NLRC4-dependent caspase-1 activation. Moreover, in all P. aeruginosa studies, IL-1beta production was attenuated in NLRC4(-/-) mice; however, the role of IL-1beta in NLRC4-mediated innate immunity in the lungs against a nonflagellated bacterium was not explored. In this article, we report that NLRC4 is important for host survival and bacterial clearance, as well as neutrophil-mediated inflammation in the lungs following Klebsiella pneumoniae infection. NLRC4 is essential for K. pneumoniae-induced production of IL-1beta, IL-17A, and neutrophil chemoattractants (keratinocyte cell-derived chemokines, MIP-2, and LPS-induced CXC chemokines) in the lungs. NLRC4 signaling in hematopoietic cells contributes to K. pneumoniae-induced lung inflammation. Furthermore, exogenous IL-1beta, but not IL-18 or IL-17A, partially rescued survival, neutrophil accumulation, and cytokine/chemokine expression in the lungs of NLRC4(-/-) mice following infectious challenge. Furthermore, IL-1R1(-/-) mice displayed a decrease in neutrophilic inflammation in the lungs postinfection. Taken together, these findings provide novel insights into the role of NLRC4 in host defense against K. pneumoniae infection. |
