Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis

Mark S. Ladinsky, Leandro P. Araujo, Xiao Zhang, John Veltri, Marta Galan-Diez, Salima Soualhi, Carolyn Lee, Koichiro Irie, Elisha Y. Pinker, Seiko Narushima, Sheila Bandyopadhyay, Manabu Nagayama, Wael Elhenawy, Brian K. Coombes, Ronaldo P. Ferraris, Kenya Honda, Iliyan D. Iliev, Nan Gao, Pamela J. Bjorkman, Ivaylo I. Ivanov

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Commensal bacteria influence host physiology, without invading host tissues. We show that proteins from segmented filamentous bacteria (SFB) are transferred into intestinal epithelial cells (IECs) through adhesion-directed endocytosis that is distinct from the clathrin-dependent endocytosis of invasive pathogens. This process transfers microbial cell wall–associated proteins, including an antigen that stimulates mucosal T helper 17 (T H 17) cell differentiation, into the cytosol of IECs in a cell division control protein 42 homolog (CDC42)–dependent manner. Removal of CDC42 activity in vivo led to disruption of endocytosis induced by SFB and decreased epithelial antigen acquisition, with consequent loss of mucosal T H 17 cells. Our findings demonstrate direct communication between a resident gut microbe and the host and show that under physiological conditions, IECs acquire antigens from commensal bacteria for generation of T cell responses to the resident microbiota.

Original languageEnglish
Article numbereaat4042
JournalScience
Volume363
Issue number6431
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Endocytosis
Homeostasis
Epithelial Cells
Bacteria
T-Lymphocytes
Antigens
Cell Division
Proteins
Clathrin
Microbiota
Cell Adhesion
Cytosol
Cell Differentiation

ASJC Scopus subject areas

  • General

Cite this

Ladinsky, M. S., Araujo, L. P., Zhang, X., Veltri, J., Galan-Diez, M., Soualhi, S., ... Ivanov, I. I. (2019). Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis. Science, 363(6431), [eaat4042]. https://doi.org/10.1126/science.aat4042

Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis. / Ladinsky, Mark S.; Araujo, Leandro P.; Zhang, Xiao; Veltri, John; Galan-Diez, Marta; Soualhi, Salima; Lee, Carolyn; Irie, Koichiro; Pinker, Elisha Y.; Narushima, Seiko; Bandyopadhyay, Sheila; Nagayama, Manabu; Elhenawy, Wael; Coombes, Brian K.; Ferraris, Ronaldo P.; Honda, Kenya; Iliev, Iliyan D.; Gao, Nan; Bjorkman, Pamela J.; Ivanov, Ivaylo I.

In: Science, Vol. 363, No. 6431, eaat4042, 01.01.2019.

Research output: Contribution to journalArticle

Ladinsky, MS, Araujo, LP, Zhang, X, Veltri, J, Galan-Diez, M, Soualhi, S, Lee, C, Irie, K, Pinker, EY, Narushima, S, Bandyopadhyay, S, Nagayama, M, Elhenawy, W, Coombes, BK, Ferraris, RP, Honda, K, Iliev, ID, Gao, N, Bjorkman, PJ & Ivanov, II 2019, 'Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis', Science, vol. 363, no. 6431, eaat4042. https://doi.org/10.1126/science.aat4042
Ladinsky MS, Araujo LP, Zhang X, Veltri J, Galan-Diez M, Soualhi S et al. Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis. Science. 2019 Jan 1;363(6431). eaat4042. https://doi.org/10.1126/science.aat4042
Ladinsky, Mark S. ; Araujo, Leandro P. ; Zhang, Xiao ; Veltri, John ; Galan-Diez, Marta ; Soualhi, Salima ; Lee, Carolyn ; Irie, Koichiro ; Pinker, Elisha Y. ; Narushima, Seiko ; Bandyopadhyay, Sheila ; Nagayama, Manabu ; Elhenawy, Wael ; Coombes, Brian K. ; Ferraris, Ronaldo P. ; Honda, Kenya ; Iliev, Iliyan D. ; Gao, Nan ; Bjorkman, Pamela J. ; Ivanov, Ivaylo I. / Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis. In: Science. 2019 ; Vol. 363, No. 6431.
@article{bfb97f80d3a2487886360a6861463261,
title = "Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis",
abstract = "Commensal bacteria influence host physiology, without invading host tissues. We show that proteins from segmented filamentous bacteria (SFB) are transferred into intestinal epithelial cells (IECs) through adhesion-directed endocytosis that is distinct from the clathrin-dependent endocytosis of invasive pathogens. This process transfers microbial cell wall–associated proteins, including an antigen that stimulates mucosal T helper 17 (T H 17) cell differentiation, into the cytosol of IECs in a cell division control protein 42 homolog (CDC42)–dependent manner. Removal of CDC42 activity in vivo led to disruption of endocytosis induced by SFB and decreased epithelial antigen acquisition, with consequent loss of mucosal T H 17 cells. Our findings demonstrate direct communication between a resident gut microbe and the host and show that under physiological conditions, IECs acquire antigens from commensal bacteria for generation of T cell responses to the resident microbiota.",
author = "Ladinsky, {Mark S.} and Araujo, {Leandro P.} and Xiao Zhang and John Veltri and Marta Galan-Diez and Salima Soualhi and Carolyn Lee and Koichiro Irie and Pinker, {Elisha Y.} and Seiko Narushima and Sheila Bandyopadhyay and Manabu Nagayama and Wael Elhenawy and Coombes, {Brian K.} and Ferraris, {Ronaldo P.} and Kenya Honda and Iliev, {Iliyan D.} and Nan Gao and Bjorkman, {Pamela J.} and Ivanov, {Ivaylo I.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1126/science.aat4042",
language = "English",
volume = "363",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6431",

}

TY - JOUR

T1 - Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis

AU - Ladinsky, Mark S.

AU - Araujo, Leandro P.

AU - Zhang, Xiao

AU - Veltri, John

AU - Galan-Diez, Marta

AU - Soualhi, Salima

AU - Lee, Carolyn

AU - Irie, Koichiro

AU - Pinker, Elisha Y.

AU - Narushima, Seiko

AU - Bandyopadhyay, Sheila

AU - Nagayama, Manabu

AU - Elhenawy, Wael

AU - Coombes, Brian K.

AU - Ferraris, Ronaldo P.

AU - Honda, Kenya

AU - Iliev, Iliyan D.

AU - Gao, Nan

AU - Bjorkman, Pamela J.

AU - Ivanov, Ivaylo I.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Commensal bacteria influence host physiology, without invading host tissues. We show that proteins from segmented filamentous bacteria (SFB) are transferred into intestinal epithelial cells (IECs) through adhesion-directed endocytosis that is distinct from the clathrin-dependent endocytosis of invasive pathogens. This process transfers microbial cell wall–associated proteins, including an antigen that stimulates mucosal T helper 17 (T H 17) cell differentiation, into the cytosol of IECs in a cell division control protein 42 homolog (CDC42)–dependent manner. Removal of CDC42 activity in vivo led to disruption of endocytosis induced by SFB and decreased epithelial antigen acquisition, with consequent loss of mucosal T H 17 cells. Our findings demonstrate direct communication between a resident gut microbe and the host and show that under physiological conditions, IECs acquire antigens from commensal bacteria for generation of T cell responses to the resident microbiota.

AB - Commensal bacteria influence host physiology, without invading host tissues. We show that proteins from segmented filamentous bacteria (SFB) are transferred into intestinal epithelial cells (IECs) through adhesion-directed endocytosis that is distinct from the clathrin-dependent endocytosis of invasive pathogens. This process transfers microbial cell wall–associated proteins, including an antigen that stimulates mucosal T helper 17 (T H 17) cell differentiation, into the cytosol of IECs in a cell division control protein 42 homolog (CDC42)–dependent manner. Removal of CDC42 activity in vivo led to disruption of endocytosis induced by SFB and decreased epithelial antigen acquisition, with consequent loss of mucosal T H 17 cells. Our findings demonstrate direct communication between a resident gut microbe and the host and show that under physiological conditions, IECs acquire antigens from commensal bacteria for generation of T cell responses to the resident microbiota.

UR - http://www.scopus.com/inward/record.url?scp=85062594747&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062594747&partnerID=8YFLogxK

U2 - 10.1126/science.aat4042

DO - 10.1126/science.aat4042

M3 - Article

VL - 363

JO - Science

JF - Science

SN - 0036-8075

IS - 6431

M1 - eaat4042

ER -