title: Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome.
abstract: While conventional pathogenic protists have been extensively studied, there is an underappreciated constitutive protist microbiota that is an integral part of the vertebrate microbiome. The impact of these species on the host and their potential contributions to mucosal immune homeostasis remain poorly studied. Here, we show that the protozoan Tritrichomonas musculis activates the host epithelial inflammasome to induce IL-18 release. Epithelial-derived IL-18 promotes dendritic cell-driven Th1 and Th17 immunity and confers dramatic protection from mucosal bacterial infections. Along with its role as a "protistic" antibiotic, colonization with T. musculis exacerbates the development of T-cell-driven colitis and sporadic colorectal tumors. Our findings demonstrate a novel mutualistic host-protozoan interaction that increases mucosal host defenses at the cost of an increased risk of inflammatory disease.
authors.affiliation: Department of Oncological Science, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA; The Immunological Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA.
authors.forename: Aleksey
authors.initials: A
authors.lastname: Chudnovskiy
authors.affiliation: Department of Oncological Science, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA; The Immunological Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Mortha
authors.affiliation: Department of Oncological Science, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA; The Immunological Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA.
authors.forename: Veronika
authors.initials: V
authors.lastname: Kana
authors.affiliation: Molecular Parasitology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kennard
authors.affiliation: Grupo de Investigaciones Microbiologicas-UR (GIMUR), Universidad del Rosario, Bogotá, Colombia; Molecular Parasitology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Juan David
authors.initials: JD
authors.lastname: Ramirez
authors.affiliation: The Immunological Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA; Department of Genetics & Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA.
authors.forename: Adeeb
authors.initials: A
authors.lastname: Rahman
authors.affiliation: Department of Oncological Science, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA; The Immunological Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA.
authors.forename: Romain
authors.initials: R
authors.lastname: Remark
authors.affiliation: Department of Genetics & Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Mogno
authors.affiliation: The Immunological Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA.
authors.forename: Ruby
authors.initials: R
authors.lastname: Ng
authors.affiliation: The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA; The Immunological Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA.
authors.forename: Sasha
authors.initials: S
authors.lastname: Gnjatic
authors.affiliation: Department of Oncological Science, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA; The Immunological Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA.
authors.forename: El-Ad David
authors.initials: ED
authors.lastname: Amir
authors.affiliation: The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Solovyov
authors.affiliation: The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Greenbaum
authors.affiliation: The Immunological Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA; Department of Genetics & Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Clemente
authors.affiliation: The Immunological Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA; Department of Genetics & Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA.
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Faith
authors.affiliation: Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA; NIAID Microbiome Program, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
authors.affiliation: Molecular Parasitology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Grigg
authors.affiliation: Department of Oncological Science, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA; The Immunological Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA. Electronic address: miriam.merad@mssm.edu.
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
mesh_terms: D000818:Animals; D003092:Colitis / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology*; D004029:Dientamoeba / Q000276:immunology; D006790:Host-Parasite Interactions; D018928:Immunity, Mucosal; D058847:Inflammasomes / Q000276:immunology*; D020382:Interleukin-18 / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000276:immunology*; D012480:Salmonella Infections / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology; D013559:Symbiosis; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D014244:Trichomonas / Q000276:immunology*; D014245:Trichomonas Infections / Q000276:immunology*
chemical_list: D058847:Inflammasomes; D020382:Interleukin-18
keywords: IL-18; IL-1b; Tritrichomonas musculis; colon cancer; commensal protist; gut dendritic cells; gut macrophages; inflammasome; intestinal bacterial infection; microbiome