Gasdermins against intracellular bacterial pathogens

Intracellular bacterial pathogens can cause high levels of morbidity and mortality in humans. Host immune responses that protect against these infections include pyroptosis, a form of lytic cell death caused by the insertion of large gasdermin (GSDM) pores into the host plasma membrane. Here we review recent advances in our understanding of how the five GSDM proteins, GSDMA-E, are activated by distinct signalling pathways. Pyroptosis can both eliminate intracellular niches and release cytosolic interleukin-1 family cytokines that further prime host immune responses against the invading pathogen. Because pyroptosis targets microbes, host-adapted intracellular pathogens have evolved strategies to efficiently subvert it. However, environmental pathogens fail to evade, making pyroptosis a potent barrier against infection. We summarize recent findings for the host-adapted bacterial pathogens Shigella flexneri, Salmonella enterica serovar Typhimurium and Mycobacterium tuberculosis, contrasted with the environmental bacteria Burkholderia thailandensis and Chromobacterium violaceum.