Hosted by: Vern Carruthers
Microbiology and Immunology Seminar Series
Abstract: Infection with intracellular pathogens such as the parasite Toxoplasma gondii and the bacterium Salmonella typhimurium generates the cytokine interferon gamma (IFN). IFN stimulates cells to upregulate host defense proteins, amongst them the interferon-inducible guanylate binding proteins (GBPs). GBPs promote cell-intrinsic defense by targeting pathogens and pathogen-containing vacuoles for membrane-disruption that releases microbial molecules to induce host cell death. GBP1 mediates pyroptosis or atypical apoptosis of Salmonella- or Toxoplasma-infected human macrophages, respectively. We have developed an artificial intelligence-driven image analysis pipeline (HRMAn, Host Response to Microbe Infection) enabling us to conduct high throughput single-cell analysis of these host defense mechanisms. Combined with mechanistic cellular studies and unbiased mass spectrometry approaches, we are addressing the host cell intrinsic defense pathways driven by GBPs in response to these two evolutionarily divergent pathogens.