| First Author | Shutinoski B | Year | 2020 |
| Journal | Microbes Infect | Volume | 22 |
| Issue | 1 | Pages | 40-45 |
| PubMed ID | 31430539 | Mgi Jnum | J:298109 |
| Mgi Id | MGI:6472142 | Doi | 10.1016/j.micinf.2019.08.002 |
| Citation | Shutinoski B, et al. (2020) Ripk3 licenced protection against microbial infection in the absence of Caspase1-11 inflammasome. Microbes Infect 22(1):40-45 |
| abstractText | Receptor interacting protein kinase 3 (Ripk3) is a signal relay protein involved in initiation of programmed cell death (necroptosis) and modulation of inflammasome activation. While caspase 1 and 11 are pro-inflammatory caspases responsible for unleashing inflammation and cell death by enzymatic activation of the executioners of inflammation and cell death (pyroptosis). Upon Salmonella infection, the host mounts a pro-inflammatory response which require Ripk3 and Caspase1/11. Here we show that bone marrow derived macrophages with combined deficiency of Ripk3 and Casp1/11 are highly resistant to Salmonella induced cell death, and that these macrophages show an anti-inflammatory cytokine profile. We confirm what was previously known that mice deficient in Casp1/11 have impaired ability to control Salmonella burden, and that the absence of Ripk3 alone does not influence the innate immune responses to Salmonella infection. However, we describe a synergistic role of Ripk3 and Casp1/11 in regulating Salmonella in vivo burden and that Ripk3-dependent host protection in the absence of Casp1/11 is evident during infection by sifA-expressing Salmonella. In summary, we show that the Ripk3 protection to Salmonella infection is obscured by presence of Caspase 1/11 and that the Ripk3-dependent protection requires a phagosome-bound Salmonella. |
