| First Author | van Lieshout MH | Year | 2014 |
| Journal | Am J Respir Cell Mol Biol | Volume | 50 |
| Issue | 4 | Pages | 699-712 |
| PubMed ID | 24164497 | Mgi Jnum | J:232091 |
| Mgi Id | MGI:5775891 | Doi | 10.1165/rcmb.2013-0015OC |
| Citation | van Lieshout MH, et al. (2014) NLRP3 and ASC differentially affect the lung transcriptome during pneumococcal pneumonia. Am J Respir Cell Mol Biol 50(4):699-712 |
| abstractText | Streptococcus pneumoniae is the most frequently isolated causative pathogen of community-acquired pneumonia, a leading cause of mortality worldwide. Inflammasomes are multiprotein complexes that play crucial roles in the regulation of inflammation. Nod-like receptor family, pyrin domain containing (NLRP) 3 is a sensor that functions in a single inflammasome, whereas adaptor apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) is a common adaptor of several inflammasomes. We investigated the role of NLRP3 and ASC during S. pneumoniae pneumonia by comparing bacterial growth and spreading, and host innate immune responses in wild-type mice and mice deficient for either NLRP3 (Nlrp3(-/-)) or ASC (Asc(-/-)). Asc(-/-) mice had increased bacterial dissemination and lethality compared with Nlrp3(-/-) mice, although the cytokine response was impaired in both mouse strains. By detailed analysis of the early inflammatory response in the lung by whole-genome transcriptional profiling, we identified several mediators that were differentially expressed between Nlrp3(-/-) and Asc(-/-) mice. Of these, IL-17, granulocyte/macrophage colony-stimulating factor, and integrin-alphaM were significantly attenuated in Asc(-/-) relative to Nlrp3(-/-) mice, as well as a number of genes involved in the adaptive immune response. These differences may explain the increased susceptibility of Asc(-/ -) mice during S. pneumoniae infection, and suggest that either ASC-dependent NLRP3-independent inflammasomes or inflammasome-independent ASC functions may be involved. |
