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

• Published in: Cell Vol. 167; no. 2; pp. 444 - 456.e14
• Main Authors: Chudnovskiy, Aleksey, Mortha, Arthur, Kana, Veronika, Kennard, Andrea, Ramirez, Juan David, Rahman, Adeeb, Remark, Romain, Mogno, Ilaria, Ng, Ruby, Gnjatic, Sasha, Amir, El-ad David, Solovyov, Alexander, Greenbaum, Benjamin, Clemente, Jose, Faith, Jeremiah, Belkaid, Yasmine, Grigg, Michael E., Merad, Miriam
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.10.2016
• Subjects: Animals; Colitis - immunology; Colitis - microbiology; Colitis - parasitology; colon cancer; commensal protist; Dientamoeba - immunology; gut dendritic cells; gut macrophages; Host-Parasite Interactions; IL-18; IL-1b; Immunity, Mucosal; inflammasome; Inflammasomes - immunology; Interleukin-18 - immunology; intestinal bacterial infection; Intestinal Mucosa - immunology; Intestinal Mucosa - microbiology; Intestinal Mucosa - parasitology; Mice; Mice, Inbred C57BL; microbiome; Microbiota - immunology; Salmonella Infections - immunology; Salmonella typhimurium - immunology; Symbiosis; Th1 Cells - immunology; Th17 Cells - immunology; Trichomonas - immunology; Trichomonas Infections - immunology; Tritrichomonas musculis; intestinal bacterial infection; inflammasome; IL-18; colon cancer; commensal protist; gut dendritic cells; IL-1b; Tritrichomonas musculis; microbiome; gut macrophages
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2016.08.076

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. [Display omitted] •A murine commensal protist named T.mu modulates colonic mucosal immunity•T.mu reprograms colonic immunity via IRF8- and IRF4-dependent dendritic cells•T.mu-driven IL-18 protects against enteric bacteria but promotes CRC progression•A T.mu-related protist is highly prevalent in the stools of healthy individuals Expanding the vertebrate microbiota diversity: a mutualistic protozoan acts as a “protistic antibiotic,” protecting the intestinal mucosa against bacterial infections.