1. Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome
- Author
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Jose C. Clemente, Ruby Ng, Adeeb Rahman, Romain Remark, Jeremiah J. Faith, Benjamin Greenbaum, El-ad David Amir, Michael E. Grigg, Veronika Kana, Andrea Kennard, Miriam Merad, Sasha Gnjatic, Alexander Solovyov, Aleksey Chudnovskiy, Juan David Ramírez, Ilaria Mogno, Arthur Mortha, and Yasmine Belkaid
- Subjects
0301 basic medicine ,Salmonella typhimurium ,medicine.drug_class ,Inflammasomes ,Antibiotics ,Trichomonas Infections ,Disease ,Inbred C57BL ,General Biochemistry, Genetics and Molecular Biology ,Host-Parasite Interactions ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immunity ,parasitic diseases ,medicine ,Animals ,Microbiome ,Colitis ,Intestinal Mucosa ,Symbiosis ,Dientamoeba ,Immunity, Mucosal ,Tritrichomonas ,Mucosal ,biology ,Host (biology) ,Microbiota ,Interleukin-18 ,Inflammasome ,Th1 Cells ,biology.organism_classification ,medicine.disease ,Mice, Inbred C57BL ,030104 developmental biology ,030220 oncology & carcinogenesis ,Immunology ,Salmonella Infections ,Trichomonas ,Th17 Cells ,medicine.drug - Abstract
Summary 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.
- Published
- 2016