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

Resultado de la investigación: Contribución a RevistaArtículo

84 Citas (Scopus)

Resumen

Mientras que los protistas patógenos convencionales han sido ampliamente estudiados, existe una microbiota protista constitutiva poco apreciada que es una parte integral del microbioma vertebrado. El impacto de estas especies en el huésped y su potencial contribución a la homeostasis inmune de la mucosa sigue siendo poco estudiado. Aquí, mostramos que el protozoario Tritrichomonas musculis activa el inflamación epitelial del huésped para inducir la liberación de IL-18. La IL-18 derivada del epitelio promueve la inmunidad a las células dendríticas Th1 y Th17 y confiere una protección dramática contra las infecciones bacterianas de la mucosa. Junto con su papel como antibiótico "protético", la colonización con T. musculis exacerba el desarrollo de colitis por células T y tumores colorrectales esporádicos. Nuestros hallazgos demuestran una novedosa interacción entre el huésped y el protozoario que aumenta las defensas del huésped de la mucosa a costa de un mayor riesgo de enfermedad inflamatoria".
Idioma originalEnglish (US)
Páginas (desde-hasta)444-456.e14
Número de páginas13
PublicaciónCell
DOI
EstadoPublished - oct 6 2016

Huella dactilar

Inflammasomes
Interleukin-18
Microbiota
Tritrichomonas
Chemical activation
T-cells
Colitis
Infection
Bacterial Infections
Dendritic Cells
Vertebrates
Tumors
Colorectal Neoplasms
Immunity
Homeostasis
Anti-Bacterial Agents
T-Lymphocytes

Citar esto

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. / Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome. En: Cell. 2016 ; pp. 444-456.e14.
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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 “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.",
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",
year = "2016",
month = "10",
day = "6",
doi = "10.1016/j.cell.2016.08.076",
language = "English (US)",
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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, pp. 444-456.e14. https://doi.org/10.1016/j.cell.2016.08.076

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

En: Cell, 06.10.2016, p. 444-456.e14.

Resultado de la investigación: Contribución a RevistaArtículo

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

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.

U2 - 10.1016/j.cell.2016.08.076

DO - 10.1016/j.cell.2016.08.076

M3 - Article

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SP - 444-456.e14

JO - Cell

JF - Cell

SN - 0092-8674

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