CX3CR1+, mononuclear phagocytes control immunity to intestinal fungi

Irina Leonardi, Xin Li, Alexa Semon, Dalin Li, Itai Doron, Gregory Putzel, Agnieszka Bar, Daniel Prieto, Maria Rescigno, Dermot P.B. McGovern, Jesus Pla, Iliyan D. Iliev

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Intestinal fungi are an important component of the microbiota, and recent studies have unveiled their potential in modulating host immune homeostasis and inflammatory disease. Nonetheless, the mechanisms governing immunity to gut fungal communities (mycobiota) remain unknown. We identified CX3CR1+, mononuclear phagocytes (MNPs) as being essential for the initiation of innate and adaptive immune responses to intestinal fungi. CX3CR1+, MNPs express antifungal receptors and activate antifungal responses in a Syk-dependent manner. Genetic ablation of CX3CR1+, MNPs in mice led to changes in gut fungal communities and to severe colitis that was rescued by antifungal treatment. In Crohn's disease patients, a missense mutation in the gene encoding CX3CR1 was identified and found to be associated with impaired antifungal responses. These results unravel a role of CX3CR1+, MNPs in mediating interactions between intestinal mycobiota and host immunity at steady state and during inflammatory disease.

Original languageEnglish
Pages (from-to)232-236
Number of pages5
JournalScience
Volume359
Issue number6372
DOIs
Publication statusPublished - Jan 12 2018

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Phagocytes
Immunity
Fungi
Microbiota
Adaptive Immunity
Missense Mutation
Colitis
Innate Immunity
Crohn Disease
Homeostasis
Genes
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Leonardi, I., Li, X., Semon, A., Li, D., Doron, I., Putzel, G., ... Iliev, I. D. (2018). CX3CR1+, mononuclear phagocytes control immunity to intestinal fungi. Science, 359(6372), 232-236. https://doi.org/10.1126/science.aao1503

CX3CR1+, mononuclear phagocytes control immunity to intestinal fungi. / Leonardi, Irina; Li, Xin; Semon, Alexa; Li, Dalin; Doron, Itai; Putzel, Gregory; Bar, Agnieszka; Prieto, Daniel; Rescigno, Maria; McGovern, Dermot P.B.; Pla, Jesus; Iliev, Iliyan D.

In: Science, Vol. 359, No. 6372, 12.01.2018, p. 232-236.

Research output: Contribution to journalArticle

Leonardi, I, Li, X, Semon, A, Li, D, Doron, I, Putzel, G, Bar, A, Prieto, D, Rescigno, M, McGovern, DPB, Pla, J & Iliev, ID 2018, 'CX3CR1+, mononuclear phagocytes control immunity to intestinal fungi', Science, vol. 359, no. 6372, pp. 232-236. https://doi.org/10.1126/science.aao1503
Leonardi I, Li X, Semon A, Li D, Doron I, Putzel G et al. CX3CR1+, mononuclear phagocytes control immunity to intestinal fungi. Science. 2018 Jan 12;359(6372):232-236. https://doi.org/10.1126/science.aao1503
Leonardi, Irina ; Li, Xin ; Semon, Alexa ; Li, Dalin ; Doron, Itai ; Putzel, Gregory ; Bar, Agnieszka ; Prieto, Daniel ; Rescigno, Maria ; McGovern, Dermot P.B. ; Pla, Jesus ; Iliev, Iliyan D. / CX3CR1+, mononuclear phagocytes control immunity to intestinal fungi. In: Science. 2018 ; Vol. 359, No. 6372. pp. 232-236.
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