| First Author | Muendlein HI | Year | 2022 |
| Journal | Proc Natl Acad Sci U S A | Volume | 119 |
| Issue | 24 | Pages | e2113872119 |
| PubMed ID | 35666872 | Mgi Jnum | J:341787 |
| Mgi Id | MGI:7311523 | Doi | 10.1073/pnas.2113872119 |
| Citation | Muendlein HI, et al. (2022) ZBP1 promotes inflammatory responses downstream of TLR3/TLR4 via timely delivery of RIPK1 to TRIF. Proc Natl Acad Sci U S A 119(24):e2113872119 |
| abstractText | SignificanceWhile ZBP1 is well documented to drive cell death in response to viruses, its role in the context of Toll-like receptor (TLR)-mediated immune activation remains less defined. Here, we show that ZBP1 promotes inflammation in response to bacterial lipopolysaccharide (LPS) or double-stranded RNA (dsRNA). In a dose dependent manner, ZBP1 promotes the recruitment of RIPK1 to the TLR3/4 adaptor TRIF, activating downstream inflammatory signaling. ZBP1 plays a crucial role in TRIF-dependent responses in vivo, as Zbp1(-/-) mice exhibited resistance to LPS-induced hypothermia and attenuated inflammatory responses to dsRNA. Our findings suggest that ZBP1 plays a synergistic role in the immune response by driving inflammation downstream of TLRs in response to bacterial and viral components. |
