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

doi:10.1016/j.cell.2016.08.076

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 Journal › Research Article › peer-review

271 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 language	English (US)
Pages (from-to)	444-456.e14
Journal	Cell
Volume	167
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2016.08.076
State	Published - Oct 6 2016
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

All Science Journal Classification (ASJC) codes

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2016.08.076

Cite this

Chudnovskiy, A., Mortha, A., Kana, V., Kennard, A., Ramirez, J. D., Rahman, A., Remark, R., Mogno, I., Ng, R., Gnjatic, S., Amir, E. A. D., Solovyov, A., Greenbaum, B., Clemente, J., Faith, J., Belkaid, Y., Grigg, M. E., & Merad, M. (2016). Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome. Cell, 167(2), 444-456.e14. https://doi.org/10.1016/j.cell.2016.08.076

@article{d950c4cee242429ab9b3ed5c622f613c,

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 {\textquotedblleft}protistic{\textquotedblright} 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.",

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

note = "Funding Information: We thank the M.M. laboratory for helpful discussions and input. We would like to thank Fiona Desland for critical review of the manuscript. We would like to thank Jordi Ochando and the Flow Cytometry facility for their excellent technical support and assistance with cell sorting. We would like to thank Steve Porcella (Genomics Unit, RTB, Rocky Mountain Labs, NIAID), Mariam Quinones (Bioinformatics and Computational Biology Branch, NIAID), and Jacquice Davis (NIAID Microbiome Program) for their assistance with metagenomic and analysis. This study used the Nephele platform from the NIAID Office of Cyber Infrastructure and Computational Biology (OCICB) in Bethesda, MD. M.M. is funded by NIH grants R01 CA154947A, R01 CA173861, and U01 AI095611. This work was supported in part by the National Institute of Allergy and Infectious Diseases, NIH (Y.B. and M.E.G.). M.E.G. Is a Scholar of the Canadian Institute for Advanced Research (CIFAR) Integrated Microbial Biodiversity Program. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = oct,

day = "6",

doi = "10.1016/j.cell.2016.08.076",

language = "English (US)",

volume = "167",

pages = "444--456.e14",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier BV",

number = "2",

}

Chudnovskiy, A, Mortha, A, Kana, V, Kennard, A, Ramirez, JD, Rahman, A, Remark, R, Mogno, I, Ng, R, Gnjatic, S, Amir, EAD, Solovyov, A, Greenbaum, B, Clemente, J, Faith, J, Belkaid, Y, Grigg, ME & Merad, M 2016, 'Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome', Cell, vol. 167, no. 2, pp. 444-456.e14. https://doi.org/10.1016/j.cell.2016.08.076

TY - JOUR

T1 - Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome

AU - Chudnovskiy, Aleksey

AU - Mortha, Arthur

AU - Kana, Veronika

AU - Kennard, Andrea

AU - Ramirez, Juan David

AU - Rahman, Adeeb

AU - Remark, Romain

AU - Mogno, Ilaria

AU - Ng, Ruby

AU - Gnjatic, Sasha

AU - Amir, El ad David

AU - Solovyov, Alexander

AU - Greenbaum, Benjamin

AU - Clemente, Jose

AU - Faith, Jeremiah

AU - Belkaid, Yasmine

AU - Grigg, Michael E.

AU - Merad, Miriam

N1 - Funding Information: We thank the M.M. laboratory for helpful discussions and input. We would like to thank Fiona Desland for critical review of the manuscript. We would like to thank Jordi Ochando and the Flow Cytometry facility for their excellent technical support and assistance with cell sorting. We would like to thank Steve Porcella (Genomics Unit, RTB, Rocky Mountain Labs, NIAID), Mariam Quinones (Bioinformatics and Computational Biology Branch, NIAID), and Jacquice Davis (NIAID Microbiome Program) for their assistance with metagenomic and analysis. This study used the Nephele platform from the NIAID Office of Cyber Infrastructure and Computational Biology (OCICB) in Bethesda, MD. M.M. is funded by NIH grants R01 CA154947A, R01 CA173861, and U01 AI095611. This work was supported in part by the National Institute of Allergy and Infectious Diseases, NIH (Y.B. and M.E.G.). M.E.G. Is a Scholar of the Canadian Institute for Advanced Research (CIFAR) Integrated Microbial Biodiversity Program. Publisher Copyright: © 2016 Elsevier Inc.

PY - 2016/10/6

Y1 - 2016/10/6

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84990846993

UR - https://www.scopus.com/pages/publications/84990846993#tab=citedBy

U2 - 10.1016/j.cell.2016.08.076

DO - 10.1016/j.cell.2016.08.076

M3 - Research Article

C2 - 27716507

AN - SCOPUS:84990846993

SN - 0092-8674

VL - 167

SP - 444-456.e14

JO - Cell

JF - Cell

IS - 2

ER -

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

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