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 language | English |
|---|---|
| Article number | eaat4042 |
| Journal | Science |
| Volume | 363 |
| Issue number | 6431 |
| DOIs | |
| Publication status | Published - 2019 Jan 1 |
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ASJC Scopus subject areas
- General
Cite this
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 journal › Article
}
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
C2 - 30846568
AN - SCOPUS:85062594747
VL - 363
JO - Science
JF - Science
SN - 0036-8075
IS - 6431
M1 - eaat4042
ER -