Phagocytes produce prostaglandin E2 in response to cytosolic Listeria monocytogenes

• DOI: 10.1371/journal.ppat.1009493
• Publication Date: 2021-09-24T11:25:03Z
• Authors: Courtney E. McDougal; Zachary T. Morrow; Tighe Christopher; Seonyoung Kim; Drake Carter; David M. Stevenson; Daniel Amador-Noguez; Mark J. Miller; John-Demian Sauer
• Keywords: Priming (agriculture); CD11c

Listeria monocytogenes is an intracellular bacterium that elicits robust CD8 + T-cell responses. Despite the ongoing development of L . -based platforms as cancer vaccines, our understanding how drives responses remains incomplete. One overarching hypothesis activation cytosolic innate pathways critical for immunity, strains are unable to access cytosol fail elicit and in fact inhibit optimal priming. Counterintuitively, however, known pathways, such inflammasome type I IFN, lead impaired immunity. Conversely, production prostaglandin E 2 (PGE ) downstream cyclooxygenase-2 (COX-2) essential Here, we demonstrate vacuole-constrained reduced PGE compared wild-type macrophages dendritic cells ex vivo In , infection with leads 10-fold increases early during whereas induce over mock-immunized controls. Mice deficient COX-2 specifically Lyz2 or CD11c produce less suggesting these cell subsets contribute levels while depletion phagocytes clodronate abolishes completely. Taken together, this work demonstrates by depends on cytosol, one reason required prime may be facilitate