JCSMR School Seminar Series - Myeloid cell identity shapes cell death decisions during inflammasome signalling

Dr Kate Schroder, Institute of Molecular Bioscience, University of Queensland, Brisbane, QLD

Macrophage and dendritic cell inflammasomes drive potent innate immune responses against intracellular pathogens, by eliciting rapid caspase-1-dependent pro-inflammatory cytokine production (e.g. interleukins (IL)-1β and -18 and pyroptotic cell death, as well as caspase-8-directed apoptotic cell death. The contribution of other cell types to inflammasome-mediated host defense had not been examined in detail. We recently discovered that neutrophils, typically viewed as cellular targets of inflammasome-dependent IL-1βthemselves signal via a variety of inflammasomes, and are a major cell compartment for IL-1βproduction during in vivo infection with Salmonella. Importantly, unlike macrophages, neutrophils do not undergo pyroptosis upon in vitro or in vivo NLRC4, NLRP3 or AIM2 inflammasome activation. The ability of neutrophils to resist caspase-1-mediated death is unique amongst inflammasome-signaling cells so far described. Their continued viability allows neutrophils to sustain IL-1β production at a site of infection, and exert their crucial inflammasome-independent antimicrobial effector functions to clear infection. Additionally, we discovered that neutrophils possess a unique specialisation of the NLRP3 pathway that allows these cells to co-ordinate a neutrophil-dominated in vivo response only when it is appropriate to do so. This work reveals neutrophils as a surprising new cellular player in shaping inflammasome-mediated inflammatory responses in vivo, and highlights the major impact of myeloid cell identity on innate immune signalling pathways.

Kate Schroder heads the Inflammasome Laboratory at the Institute for Molecular Bioscience, University of Queensland, as an ARC Future Fellow. Kate’s PhD studies defined novel macrophage activation mechanisms (awarded 2005). Her subsequent postdoctoral research identified surprising inter-species divergence in the inflammatory programs of human versus mouse macrophages. As an NHMRC CJ Martin Fellow in Switzerland, Kate trained with the pioneer of inflammasome biology, Jürg Tschopp. Her current research interests include the molecular mechanisms governing inflammasome activity and caspase activation, the cellular mediators of inflammasome-dependent inflammation, and inflammasome suppression by autophagy and small molecule inhibitors.

Date & time

12–1pm 14 October 2016


The Finkel Lecture Theatre, The John Curtin School of Medical Research, Building 131 Garran Road, ANU


Host: Associate Professor Brendan McMorran


 Ceri Flowers
 +61 2 6125 2589

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