| First Author | Franchi L | Year | 2012 |
| Journal | Nat Immunol | Volume | 13 |
| Issue | 5 | Pages | 449-56 |
| PubMed ID | 22484733 | Mgi Jnum | J:185371 |
| Mgi Id | MGI:5428366 | Doi | 10.1038/ni.2263 |
| Citation | Franchi L, et al. (2012) NLRC4-driven production of IL-1beta discriminates between pathogenic and commensal bacteria and promotes host intestinal defense. Nat Immunol 13(5):449-56 |
| abstractText | Intestinal phagocytes transport oral antigens and promote immune tolerance, but their role in innate immune responses remains unclear. Here we found that intestinal phagocytes were anergic to ligands for Toll-like receptors (TLRs) or commensals but constitutively expressed the precursor to interleukin 1beta (pro-IL-1beta). After infection with pathogenic Salmonella or Pseudomonas, intestinal phagocytes produced mature IL-1beta through the NLRC4 inflammasome but did not produce tumor necrosis factor (TNF) or IL-6. BALB/c mice deficient in NLRC4 or the IL-1 receptor were highly susceptible to orogastric but not intraperitoneal infection with Salmonella. That enhanced lethality was preceded by impaired expression of endothelial adhesion molecules, lower neutrophil recruitment and poor intestinal pathogen clearance. Thus, NLRC4-dependent production of IL-1beta by intestinal phagocytes represents a specific response that discriminates pathogenic bacteria from commensal bacteria and contributes to host defense in the intestine. |
