| First Author | Chen KW | Year | 2021 |
| Journal | Proc Natl Acad Sci U S A | Volume | 118 |
| Issue | 28 | PubMed ID | 34260403 |
| Mgi Jnum | J:332350 | Mgi Id | MGI:6727132 |
| Doi | 10.1073/pnas.2101189118 | Citation | Chen KW, et al. (2021) RIPK1 activates distinct gasdermins in macrophages and neutrophils upon pathogen blockade of innate immune signaling. Proc Natl Acad Sci U S A 118(28):e2101189118 |
| abstractText | Injection of effector proteins to block host innate immune signaling is a common strategy used by many pathogenic organisms to establish an infection. For example, pathogenic Yersinia species inject the acetyltransferase YopJ into target cells to inhibit NF-kappaB and MAPK signaling. To counteract this, detection of YopJ activity in myeloid cells promotes the assembly of a RIPK1-caspase-8 death-inducing platform that confers antibacterial defense. While recent studies revealed that caspase-8 cleaves the pore-forming protein gasdermin D to trigger pyroptosis in macrophages, whether RIPK1 activates additional substrates downstream of caspase-8 to promote host defense is unclear. Here, we report that the related gasdermin family member gasdermin E (GSDME) is activated upon detection of YopJ activity in a RIPK1 kinase-dependent manner. Specifically, GSDME promotes neutrophil pyroptosis and IL-1beta release, which is critical for anti-Yersinia defense. During in vivo infection, IL-1beta neutralization increases bacterial burden in wild-type but not Gsdme-deficient mice. Thus, our study establishes GSDME as an important mediator that counteracts pathogen blockade of innate immune signaling. |
