Induction of intestinal Th17 cells by segmented filamentous bacteria.
The gastrointestinal tract of mammals is inhabited by hundreds of distinct species of commensal microorganisms that exist in a mutualistic relationship with the host. How commensal microbiota influence the host immune system is poorly understood. We show here that colonization of the small intestine of mice with a single commensal microbe, segmented filamentous bacterium (SFB), is sufficient to induce the appearance of CD4(+) T helper cells that produce IL-17 and IL-22 (Th17 cells) in the lamina propria. SFB adhere tightly to the surface of epithelial cells in the terminal ileum of mice with Th17 cells but are absent from mice that have few Th17 cells. Colonization with SFB was correlated with increased expression of genes associated with inflammation and antimicrobial defenses and resulted in enhanced resistance to the intestinal pathogen Citrobacter rodentium. Thus, manipulation of this commensal-regulated pathway may provide new opportunities for enhancing mucosal immunity and treating autoimmune disease.
Ivanov
Ivaylo I
II
Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
Atarashi
Koji
K
Manel
Nicolas
N
Brodie
Eoin L
EL
Shima
Tatsuichiro
T
Karaoz
Ulas
U
Wei
Dongguang
D
Goldfarb
Katherine C
KC
Santee
Clark A
CA
Lynch
Susan V
SV
Tanoue
Takeshi
T
Imaoka
Akemi
A
Itoh
Kikuji
K
Takeda
Kiyoshi
K
Umesaki
Yoshinori
Y
Honda
Kenya
K
Littman
Dan R
DR
D000818:Animals; D002454:Cell Differentiation; D044082:Citrobacter rodentium / Q000276:immunology; D006094:Gram-Positive Bacteria / Q000276:immunology* / Q000502:physiology; D018928:Immunity, Mucosal / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D007378:Interleukins / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology / Q000382:microbiology; D000685:Serum Amyloid A Protein / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D013559:Symbiosis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D000097043:Interleukin-22
D020381:Interleukin-17; D007378:Interleukins; D000685:Serum Amyloid A Protein; D000097043:Interleukin-22