| First Author | Janova H | Year | 2016 |
| Journal | Glia | Volume | 64 |
| Issue | 4 | Pages | 635-49 |
| PubMed ID | 26683584 | Mgi Jnum | J:229486 |
| Mgi Id | MGI:5752111 | Doi | 10.1002/glia.22955 |
| Citation | Janova H, et al. (2016) CD14 is a key organizer of microglial responses to CNS infection and injury. Glia 64(4):635-49 |
| abstractText | Microglia, innate immune cells of the CNS, sense infection and damage through overlapping receptor sets. Toll-like receptor (TLR) 4 recognizes bacterial lipopolysaccharide (LPS) and multiple injury-associated factors. We show that its co-receptor CD14 serves three non-redundant functions in microglia. First, it confers an up to 100-fold higher LPS sensitivity compared to peripheral macrophages to enable efficient proinflammatory cytokine induction. Second, CD14 prevents excessive responses to massive LPS challenges via an interferon beta-mediated feedback. Third, CD14 is mandatory for microglial reactions to tissue damage-associated signals. In mice, these functions are essential for balanced CNS responses to bacterial infection, traumatic and ischemic injuries, since CD14 deficiency causes either hypo- or hyperinflammation, insufficient or exaggerated immune cell recruitment or worsened stroke outcomes. While CD14 orchestrates functions of TLR4 and related immune receptors, it is itself regulated by TLR and non-TLR systems to thereby fine-tune microglial damage-sensing capacity upon infectious and non-infectious CNS challenges. GLIA 2016;64:635-649. |
