| First Author | Suresh R | Year | 2016 |
| Journal | J Cell Sci | Volume | 129 |
| Issue | 9 | Pages | 1928-39 |
| PubMed ID | 27006116 | Mgi Jnum | J:247280 |
| Mgi Id | MGI:5922595 | Doi | 10.1242/jcs.179291 |
| Citation | Suresh R, et al. (2016) Complement-mediated 'bystander' damage initiates host NLRP3 inflammasome activation. J Cell Sci 129(9):1928-39 |
| abstractText | Complement activation has long been associated with inflammation, primarily due to the elaboration of the complement anaphylotoxins C5a and C3a. In this work, we demonstrate that the phagocytosis of complement-opsonized particles promotes host inflammatory responses by a new mechanism that depends on the terminal complement components (C5b-C9). We demonstrate that during the phagocytosis of complement-opsonized particles, the membrane attack complex (MAC) of complement can be transferred from the activating particle to the macrophage plasma membrane by a 'bystander' mechanism. This MAC-mediated bystander damage initiates NLRP3 inflammasome activation, resulting in caspase-1 activation and IL-1beta and IL-18 secretion. Inflammasome activation is not induced when macrophages phagocytize unopsonized particles or particles opsonized with serum deficient in one of the terminal complement components. The secretion of IL-1beta and IL-18 by macrophages depends on NLRP3, ASC (also known as PYCARD) and caspase-1, as macrophages deficient in any one of these components fail to secrete these cytokines following phagocytosis. The phagocytosis of complement-opsonized particles increases leukocyte recruitment and promotes T helper 17 cell (TH17) biasing. These findings reveal a new mechanism by which complement promotes inflammation and regulates innate and adaptive immunity. |
