Innate immune recognition of a bacterial phospholipase
Inflammasome signalling is a central pillar of innate immunity leading to inflammation and cell death in response to microbes and danger signals. Toxins and other noxious compounds produced by a range of microbes and other organisms can elicit rapid inflammation and cell death in the host. However, a complete atlas of toxins capable of activating the inflammasome remains unknown. We screened a transkingdom panel of toxins and identified phospholipase C from the bacterial pathogen Clostridium perfringens as an activator of the NLRP3 inflammasome, an important component of innate immunity. This phospholipase is not a pore-forming toxin, but enters the mammalian cell via an intracellular-lysosome axis, which is distinct from many other NLRP3-activating toxins. Our work expands the growing repertoire of microbial virulence factors that can be recognised by inflammasome sensors and defines a mechanism by which a phospholipase can be recognised by the mammalian innate immune system.
Anukriti is a postdoctoral researcher and a recent PhD graduate from the laboratory of Prof. Si Ming Man at the John Curtin School of Medical Research, Australian National University. She completed her Master of Engineering in Biotechnology from the Birla Institute of Technology & Science, Pilani, India. Her research focuses on understanding the molecular mechanism of bacterial toxins in inducing cell death and inflammation. During her PhD, Anukriti identified the molecular mechanisms leading to the immune sensing of several bacterial toxins. Anukriti’s doctoral work has been published in Nature Microbiology and Nature Communications. Her research has been recognised by multiple awards from professional societies and two early career grants from the Gretel and Gordon Bootes Medical Research Foundation. She is the ACT representative at the Australian Society of Microbiology NSW/ACT branch committee and organises the ACT Microbiology Group seminar series.