The diverse roles of RIP kinases in host-pathogen interactions.

Receptor Interacting Protein Kinases (RIPKs) are cellular signaling molecules that are critical for homeostatic signaling in both communicable and non-communicable disease processes. In particular, RIPK1, RIPK2, RIPK3 and RIPK7 have emerged as key mediators of intracellular signal transduction including inflammation, autophagy and programmed cell death, and are thus essential for the early control of many diverse pathogenic organisms. In this review, we discuss the role of each RIPK in host responses to bacterial and viral pathogens, with a focus on studies that have used pathogen infection models rather than artificial stimulation with purified pathogen associated molecular patterns. We also discuss the intricate mechanisms of host evasion by pathogens that specifically target RIPKs for inactivation, and finally, we will touch on the controversial issue of drug development for kinase inhibitors to treat chronic inflammatory and neurological disorders, and the implications this may have on the outcome of pathogen infections.

Host Cell Death Responses to Non-typhoidal Salmonella Infection.

Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) is a Gram-negative bacterium with a broad host range that causes non-typhoidal salmonellosis in humans. S. Typhimurium infects epithelial cells and macrophages in the small intestine where it replicates in a specialized intracellular niche called the Salmonella-containing vacuole (SCV) and promotes inflammation of the mucosa to induce typically self-limiting gastroenteritis. Virulence and spread of the bacterium is determined in part by the host individual's ability to limit the infection through innate immune responses at the gastrointestinal mucosa, including programmed cell death. S. Typhimurium however, has evolved a myriad of mechanisms to counteract or exploit host responses through the use of Type III Secretion Systems (T3SS), which allow the translocation of virulence (effector) proteins into the host cell for the benefit of optimal bacterial replication and dissemination. T3SS effectors have been found to interact with apoptotic, necroptotic, and pyroptotic cell death cascades, interfering with both efficient clearance of the bacteria and the recruitment of neutrophils or dendritic cells to the area of infection. The interplay of host inflammation, programmed cell death responses, and bacterial defenses in the context of non-typhoidal Salmonella (NTS) infection is a continuing area of interest within the field, and as such has been reviewed here.