| First Author | Ketko AK | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 12 | Pages | e82680 |
| PubMed ID | 24312669 | Mgi Jnum | J:209745 |
| Mgi Id | MGI:5568650 | Doi | 10.1371/journal.pone.0082680 |
| Citation | Ketko AK, et al. (2013) Surfactant protein A binds flagellin enhancing phagocytosis and IL-1beta production. PLoS One 8(12):e82680 |
| abstractText | Surfactant protein A (SP-A), a pulmonary collectin, plays a role in lung innate immune host defense. In this study the role of SP-A in regulating the inflammatory response to the flagella of Pseudomonas aeruginosa (PA) was examined. Intra-tracheal infection of SP-A deficient (SP-A-/-) C57BL/6 mice with wild type flagellated PA (PAK) resulted in an increase in inflammatory cell recruitment and increase in pro-inflammatory cytokines IL-6 and TNF-alpha, which was not observed with a mutant pseudomonas lacking flagella (fliC). SP-A directly bound flagellin, via the N-linked carbohydrate moieties and collagen-like domain, in a concentration dependent manner and enhanced macrophage phagocytosis of flagellin and wild type PAK. IL-1beta was reduced in the lungs of SP-A-/- mice following PAK infection. MH-s cells, a macrophage cell line, generated greater IL-1beta when stimulated with flagellin and SP-A. Historically flagella stimulate IL-1beta production through the toll-like receptor 5 (TLR-5) pathway and through a caspase-1 activating inflammasome pathway. IL-1beta expression became non-detectable in SP-A and flagellin stimulated MH-s cells in which caspase-1 was silenced, suggesting SP-A induction of IL-1beta appears to be occurring through the inflammasome pathway. SP-A plays an important role in the pathogenesis of PA infection in the lung by binding flagellin, enhancing its phagocytosis and modifying the macrophage inflammatory response. |
