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

被引：126

作者：

Ladinsky, Mark S. ^{[1
]}

Araujo, Leandro P. ^{[2
]}

Zhang, Xiao ^{[3
]}

Veltri, John ^{[4
]}

Galan-Diez, Marta ^{[2
,12
]}

Soualhi, Salima ^{[2
,13
,14
]}

Lee, Carolyn ^{[2
]}

Irie, Koichiro ^{[2
,5
]}

Pinker, Elisha Y. ^{[2
]}

Narushima, Seiko ^{[6
]}

Bandyopadhyay, Sheila ^{[3
]}

Nagayama, Manabu ^{[6
,7
]}

Elhenawy, Wael ^{[8
]}

Coombes, Brian K. ^{[8
]}

Ferraris, Ronaldo P. ^{[4
]}

Honda, Kenya ^{[6
,9
]}

Iliev, Iliyan D. ^{[10
,11
]}

Gao, Nan ^{[3
]}

Bjorkman, Pamela J. ^{[1
]}

Ivanov, Ivaylo I. ^{[2
]}

机构：

[1] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA

[2] Columbia Univ, Dept Microbiol & Immunol, Vagelos Coll Phys & Surg, New York, NY 10032 USA

[3] Rutgers State Univ, Dept Biol Sci, Newark, NJ 07102 USA

[4] Rutgers State Univ, Dept Pharmacol Physiol & Neurosci, Newark, NJ 07103 USA

[5] Okayama Univ, Dept Prevent Dent, Grad Sch Med Dent & Pharmaceut Sci, Okayama 7008558, Japan

[6] RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa 2300045, Japan

[7] Jichi Med Univ, Dept Med, Div Gastroenterol, Shimotsuke, Tochigi 3290498, Japan

[8] McMaster Univ, Dept Biochem & Biomed Sci, Michael G DeGroote Inst Infect Dis Res, Hamilton, ON, Canada

[9] Keio Univ, Dept Microbiol & Immunol, Sch Med, Tokyo 1608582, Japan

[10] Weill Cornell Med, Dept Microbiol & Immunol, New York, NY 10065 USA

[11] Weill Cornell Med, Jill Roberts Inst Res Inflammatory Bowel Dis, New York, NY 10065 USA

[12] Columbia Univ, Dept Physiol & Cellular Biophys, Vagelos Coll Phys & Surg, New York, NY 10032 USA

[13] Boston Childrens Hosp, Div Gastroenterol, Boston, MA 02115 USA

[14] Harvard Med Sch, Boston, MA 02115 USA

来源：

SCIENCE | 2019年 / 363卷 / 6431期

关键词：

SEGMENTED FILAMENTOUS BACTERIA; TH17; CELLS; GUT; DIFFERENTIATION; METABOLITES; ADAPTATIONS; ATTACHMENT; INDUCTION; MICROBES; GENOME;

D O I：

10.1126/science.aat4042

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 (TH17) 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 TH17 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.

引用

页码：1058 / +

页数：26

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