| First Author | Shenoy AR | Year | 2012 |
| Journal | Science | Volume | 336 |
| Issue | 6080 | Pages | 481-5 |
| PubMed ID | 22461501 | Mgi Jnum | J:183942 |
| Mgi Id | MGI:5319585 | Doi | 10.1126/science.1217141 |
| Citation | Shenoy AR, et al. (2012) GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals. Science 336(6080):481-5 |
| abstractText | Inflammasomes are sensory complexes that alert the immune system to the presence of infection or tissue damage. These complexes assemble NLR (nucleotide binding and oligomerization, leucine-rich repeat) or ALR (absent in melanoma 2-like receptor) proteins to activate caspase-1 cleavage and interleukin (IL)-1beta/IL-18 secretion. Here, we identified a non-NLR/ALR human protein that stimulates inflammasome assembly: guanylate binding protein 5 (GBP5). GBP5 promoted selective NLRP3 inflammasome responses to pathogenic bacteria and soluble but not crystalline inflammasome priming agents. Generation of Gbp5(-/-) mice revealed pronounced caspase-1 and IL-1beta/IL-18 cleavage defects in vitro and impaired host defense and Nlrp3-dependent inflammatory responses in vivo. Thus, GBP5 serves as a unique rheostat for NLRP3 inflammasome activation and extends our understanding of the inflammasome complex beyond its core machinery. |
