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

Aleksey Chudnovskiy, Arthur Mortha, Veronika Kana, Andrea Kennard, Juan David Ramirez, Adeeb Rahman, Romain Remark, Ilaria Mogno, Ruby Ng, Sasha Gnjatic, El ad David Amir, Alexander Solovyov, Benjamin Greenbaum, Jose Clemente, Jeremiah Faith, Yasmine Belkaid, Michael E. Grigg, Miriam Merad

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)444-456.e14
JournalCell
Volume167
Issue number2
DOIs
StatePublished - Oct 6 2016

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome'. Together they form a unique fingerprint.

Cite this