γδ intraepithelial lymphocytes are essential mediators of host-microbial homeostasis at the intestinal mucosal surface

Anisa S. Ismail, Kari M. Severson, Shipra Vaishnava, Cassie L. Behrendt, Xiaofei Yu, Jamaal L. Benjamin, Kelly A. Ruhn, Baidong Hou, Anthony L. DeFranco, Felix Yarovinsky, Lora V. Hooper

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

The mammalian gastrointestinal tract harbors thousands of bacterial species that include symbionts as well as potential pathogens. The immune responses that limit access of these bacteria to underlying tissue remain poorly defined. Here we show that γδ intraepithelial lymphocytes (γδ IEL) of the small intestine produce innate antimicrobial factors in response to resident bacterial "pathobionts" that penetrate the intestinal epithelium. γδ IEL activation was dependent on epithelial cell-intrinsic MyD88, suggesting that epithelial cells supply microbe-dependent cues to γδ IEL. Finally, γδ T cells protect against invasion of intestinal tissues by resident bacteria specifically during the first few hours after bacterial encounter, indicating that γδ IEL occupy a unique temporal niche among intestinal immune defenses. Thus, γδ IEL detect the presence of invading bacteria through cross-talk with neighboring epithelial cells and are an essential component of the hierarchy of immune defenses that maintain homeostasis with the intestinal microbiota.

Original languageEnglish (US)
Pages (from-to)8743-8748
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number21
DOIs
StatePublished - May 24 2011

Fingerprint

Lymphokines
Homeostasis
Lymphocytes
Epithelial Cells
Bacteria
Cellular Structures
Intestinal Mucosa
Lymphocyte Activation
Small Intestine
Cues
Gastrointestinal Tract
T-Lymphocytes

Keywords

  • Antibacterial defense
  • Microbiota
  • Mucosal immunity

ASJC Scopus subject areas

  • General

Cite this

γδ intraepithelial lymphocytes are essential mediators of host-microbial homeostasis at the intestinal mucosal surface. / Ismail, Anisa S.; Severson, Kari M.; Vaishnava, Shipra; Behrendt, Cassie L.; Yu, Xiaofei; Benjamin, Jamaal L.; Ruhn, Kelly A.; Hou, Baidong; DeFranco, Anthony L.; Yarovinsky, Felix; Hooper, Lora V.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 21, 24.05.2011, p. 8743-8748.

Research output: Contribution to journalArticle

Ismail, Anisa S. ; Severson, Kari M. ; Vaishnava, Shipra ; Behrendt, Cassie L. ; Yu, Xiaofei ; Benjamin, Jamaal L. ; Ruhn, Kelly A. ; Hou, Baidong ; DeFranco, Anthony L. ; Yarovinsky, Felix ; Hooper, Lora V. / γδ intraepithelial lymphocytes are essential mediators of host-microbial homeostasis at the intestinal mucosal surface. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 21. pp. 8743-8748.
@article{9e11cc1932e14647b24be425d4fc8a8c,
title = "γδ intraepithelial lymphocytes are essential mediators of host-microbial homeostasis at the intestinal mucosal surface",
abstract = "The mammalian gastrointestinal tract harbors thousands of bacterial species that include symbionts as well as potential pathogens. The immune responses that limit access of these bacteria to underlying tissue remain poorly defined. Here we show that γδ intraepithelial lymphocytes (γδ IEL) of the small intestine produce innate antimicrobial factors in response to resident bacterial {"}pathobionts{"} that penetrate the intestinal epithelium. γδ IEL activation was dependent on epithelial cell-intrinsic MyD88, suggesting that epithelial cells supply microbe-dependent cues to γδ IEL. Finally, γδ T cells protect against invasion of intestinal tissues by resident bacteria specifically during the first few hours after bacterial encounter, indicating that γδ IEL occupy a unique temporal niche among intestinal immune defenses. Thus, γδ IEL detect the presence of invading bacteria through cross-talk with neighboring epithelial cells and are an essential component of the hierarchy of immune defenses that maintain homeostasis with the intestinal microbiota.",
keywords = "Antibacterial defense, Microbiota, Mucosal immunity",
author = "Ismail, {Anisa S.} and Severson, {Kari M.} and Shipra Vaishnava and Behrendt, {Cassie L.} and Xiaofei Yu and Benjamin, {Jamaal L.} and Ruhn, {Kelly A.} and Baidong Hou and DeFranco, {Anthony L.} and Felix Yarovinsky and Hooper, {Lora V.}",
year = "2011",
month = "5",
day = "24",
doi = "10.1073/pnas.1019574108",
language = "English (US)",
volume = "108",
pages = "8743--8748",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "21",

}

TY - JOUR

T1 - γδ intraepithelial lymphocytes are essential mediators of host-microbial homeostasis at the intestinal mucosal surface

AU - Ismail, Anisa S.

AU - Severson, Kari M.

AU - Vaishnava, Shipra

AU - Behrendt, Cassie L.

AU - Yu, Xiaofei

AU - Benjamin, Jamaal L.

AU - Ruhn, Kelly A.

AU - Hou, Baidong

AU - DeFranco, Anthony L.

AU - Yarovinsky, Felix

AU - Hooper, Lora V.

PY - 2011/5/24

Y1 - 2011/5/24

N2 - The mammalian gastrointestinal tract harbors thousands of bacterial species that include symbionts as well as potential pathogens. The immune responses that limit access of these bacteria to underlying tissue remain poorly defined. Here we show that γδ intraepithelial lymphocytes (γδ IEL) of the small intestine produce innate antimicrobial factors in response to resident bacterial "pathobionts" that penetrate the intestinal epithelium. γδ IEL activation was dependent on epithelial cell-intrinsic MyD88, suggesting that epithelial cells supply microbe-dependent cues to γδ IEL. Finally, γδ T cells protect against invasion of intestinal tissues by resident bacteria specifically during the first few hours after bacterial encounter, indicating that γδ IEL occupy a unique temporal niche among intestinal immune defenses. Thus, γδ IEL detect the presence of invading bacteria through cross-talk with neighboring epithelial cells and are an essential component of the hierarchy of immune defenses that maintain homeostasis with the intestinal microbiota.

AB - The mammalian gastrointestinal tract harbors thousands of bacterial species that include symbionts as well as potential pathogens. The immune responses that limit access of these bacteria to underlying tissue remain poorly defined. Here we show that γδ intraepithelial lymphocytes (γδ IEL) of the small intestine produce innate antimicrobial factors in response to resident bacterial "pathobionts" that penetrate the intestinal epithelium. γδ IEL activation was dependent on epithelial cell-intrinsic MyD88, suggesting that epithelial cells supply microbe-dependent cues to γδ IEL. Finally, γδ T cells protect against invasion of intestinal tissues by resident bacteria specifically during the first few hours after bacterial encounter, indicating that γδ IEL occupy a unique temporal niche among intestinal immune defenses. Thus, γδ IEL detect the presence of invading bacteria through cross-talk with neighboring epithelial cells and are an essential component of the hierarchy of immune defenses that maintain homeostasis with the intestinal microbiota.

KW - Antibacterial defense

KW - Microbiota

KW - Mucosal immunity

UR - http://www.scopus.com/inward/record.url?scp=79957701773&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79957701773&partnerID=8YFLogxK

U2 - 10.1073/pnas.1019574108

DO - 10.1073/pnas.1019574108

M3 - Article

VL - 108

SP - 8743

EP - 8748

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 21

ER -