2. Academic Validation
  3. Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome

Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome

  • Cell. 2016 Oct 6;167(2):444-456.e14. doi: 10.1016/j.cell.2016.08.076.
Aleksey Chudnovskiy 1,  Arthur Mortha 1,  Veronika Kana 1,  Andrea Kennard 2,  Juan David Ramirez 3,  Adeeb Rahman 4,  Romain Remark 1,  Ilaria Mogno 5,  Ruby Ng 6,  Sasha Gnjatic 7,  El-Ad David Amir 1,  Alexander Solovyov 8,  Benjamin Greenbaum 8,  Jose Clemente 4,  Jeremiah Faith 4,  Yasmine Belkaid 9,  Michael E Grigg 2,  Miriam Merad 10
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 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.
  • 4 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.
  • 5 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.
  • 6 The Immunological Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA.
  • 7 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.
  • 8 The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1475 Madison Avenue, New York, NY 10028, USA.
  • 9 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.
  • 10 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.
PMID: 27716507 DOI: 10.1016/j.cell.2016.08.076
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.

Keywords

IL-18; IL-1b; Tritrichomonas musculis; colon cancer; commensal protist; gut dendritic cells; gut macrophages; inflammasome; intestinal bacterial infection; microbiome.

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