TLR5 signaling stimulates the innate production of IL-17 and IL-22 by CD3(neg)CD127+ immune cells in spleen and mucosa.
In adaptive immunity, Th17 lymphocytes produce the IL-17 and IL-22 cytokines that stimulate mucosal antimicrobial defenses and tissue repair. In this study, we observed that the TLR5 agonist flagellin induced swift and transient transcription of genes encoding IL-17 and IL-22 in lymphoid, gut, and lung tissues. This innate response also temporarily enhanced the expression of genes associated with the antimicrobial Th17 signature. The source of the Th17-related cytokines was identified as novel populations of CD3(neg)CD127(+) immune cells among which CD4-expressing cells resembling lymphoid tissue inducer cells. We also demonstrated that dendritic cells are essential for expression of Th17-related cytokines and so for stimulation of innate cells. These data define that TLR-induced activation of CD3(neg)CD127(+) cells and production of Th17-related cytokines may be crucial for the early defenses against pathogen invasion of host tissues.
Van Maele
Laurye
L
Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, France.
Carnoy
Christophe
C
Cayet
Delphine
D
Songhet
Pascal
P
Dumoutier
Laure
L
Ferrero
Isabel
I
Janot
Laure
L
Erard
François
F
Bertout
Julie
J
Leger
Hélène
H
Sebbane
Florent
F
Benecke
Arndt
A
Renauld
Jean-Christophe
JC
Hardt
Wolf-Dietrich
WD
Ryffel
Bernhard
B
Sirard
Jean-Claude
JC
D000818:Animals; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D005408:Flagellin / Q000494:pharmacology; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D007082:Ileum / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000097043:Interleukin-22
D017252:CD3 Complex; D005408:Flagellin; D020381:Interleukin-17; D053699:Interleukin-7 Receptor alpha Subunit; D007378:Interleukins; D051198:Toll-Like Receptor 5; D000097043:Interleukin-22