title: Inflammasome-mediated inhibition of Listeria monocytogenes-stimulated immunity is independent of myelomonocytic function.
abstract: Activation of the Nlrc4 inflammasome results in the secretion of IL-1β and IL-18 through caspase-1 and induction of pyroptosis. L. monocytogenes engineered to activate Nlrc4 by expression of Legionella pneumophilia flagellin (L. monocytogenes L.p.FlaA) are less immunogenic for CD8(+) T cell responses than wt L. monocytogenes. It is also known that IL-1β orchestrates recruitment of myelomonocytic cells (MMC), which have been shown to interfere with T cell-dendritic cells (DC) interactions in splenic white pulp (WP), limiting T cell priming and protective immunity. We have further analyzed the role of MMCs in the immunogenicity of L. monocytogenes L.p.FlaA. We confirmed that MMCs infiltrate the WP between 24-48 hours in response to wt L. monocytogenes infection and that depletion of MMCs enhances CD8(+) T cell priming and protective memory. L. monocytogenes L.p.FlaA elicited accelerated recruitment of MMCs into the WP. While MMCs contribute to control of L. monocytogenes L.p.FlaA, MMC depletion did not increase immunogenicity of L.p.FlaA expressing strains. There was a significant decrease in L. monocytogenes L.p.FlaA in CD8α(+) DCs independent of MMCs. These findings suggest that limiting inflammasome activation is important for bacterial accumulation in CD8α(+) DCs, which are known to be critical for T cell response to L. monocytogenes.
authors.affiliation: Molecular Pathogenesis Program, The Helen L. and Martin S. Kimmel Center for Biology and Medicine at Skirball Institute of Biomolecular Medicine, New York, New York, United States of America.
authors.forename: Cassandra R
authors.initials: CR
authors.lastname: Williams
authors.affiliation: Molecular Pathogenesis Program, The Helen L. and Martin S. Kimmel Center for Biology and Medicine at Skirball Institute of Biomolecular Medicine, New York, New York, United States of America.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Dustin
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: John-Demian
authors.initials: JD
authors.lastname: Sauer
mesh_terms: D000818:Animals; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D007111:Immunity, Cellular; D058847:Inflammasomes / Q000235:genetics / Q000276:immunology*; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000378:metabolism / Q000473:pathology
chemical_list: D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; C508585:IL1B protein, human; D058847:Inflammasomes; D053583:Interleukin-1beta