Emerging Roles for RIPK1 and RIPK3 in Pathogen-Induced Cell Death and Host Immunity

Receptor-interacting protein kinases 1 and 3 (RIPK1 and RIPK3) are homologous serine-threonine kinases that were recognized for their roles in directing programmed necrotic cell death or necroptosis under a broad range of pathologic settings. Emerging evidence suggests new physiologic roles for RIPK1 and RIPK3 in mediating cell death of innate immune responses. Our review discusses current evidence on the mechanisms and the impact of RIPK1- and/or RIPK3-dependent cell death in responses to a variety of viral and bacterial pathogens. Furthermore, the discussion also summarizes emerging roles for RIPK1 and RIPK3 in other facets of host immunity, including the maintenance of epithelial barrier function and pro-inflammatory processes that may, in some cases, manifest independent of cell death. Finally, we briefly consider the therapeutic opportunities in targeting RIPK1- and RIPK3-dependent processes in infection and immunity.