Join the Department of Molecular Genetics for a special seminar hosted by EPIC member John Brumell with John-Demian Sauer who is a Professor of Medical Microbiology & Immunology at the University of Wisconsin-Madison.
Sauer will be giving a talk titled “Damage‑triggered calcium signaling: How LLO activates PGE₂ pathways to license T‑Cell immunity”. Please see the abstract below for more details:
Abstract: Recognition of invading pathogens by the innate immune system triggers a series of signaling cascades that together program appropriate adaptive immune responses. Listeria monocytogenes is a Gram positive, intracellular pathogen that triggers robust cytosolic innate immune responses upon expression of the bacterial pore forming toxin Listeriolysin O (LLO) and subsequent escape from the phagosome into the host cell cytosol. For decades it has been known that escape from the phagosome by L. monocytogenes is essential for priming of a robust protective immune response mediated by CD8+ T-cells however, what specific responses in the cytosol help promote T-cell priming has remained unknown. We recently demonstrated that production of the eicosanoid prostaglandin E2 following L. monocytogenes infection is essential for optimal CD8+ T-cell priming. We additionally demonstrated that L. monocytogenes expression of LLO is essential for PGE2 production and that phagocytes are the primary producers of PGE2 during L. monocytogenes infection in vivo. Through a series of ex vivo experiments in primary bone marrow derived macrophages we found that the function of LLO in PGE2 induction is to trigger a phagosome dependent Ca2+ flux from the Listeria containing phagosome that, in combination with ERK2 signaling, ultimately activates the cytosolic phospholipase cPLA2. Activation of cPLA2 releases arachidonic acid from the membrane allowing for the COX-2 and mPGES-1 production of PGE2. How phagocyte production of PGE2 promotes T-cell priming and how we can harness this to improve Listeria-based anti-cancer vaccines are ongoing areas of study.
Date: 4 May, 2026
Time: 9:30 – 10:30 a.m.
Location: Event room 1, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children
Registration is not required.