Identification of a novel negative role of flagellin in regulating IL-10 production.
Toll-like receptors (TLR) expressed by cells of the immune system play a central role in the generation of immune responses against pathogens. Following TLR ligation, both pro-inflammatory and anti-inflammatory mediators are produced in order to elicit an immune response that controls the microbial infection while limiting tissue damage. Among these mediators, the pro-inflammatory cytokine IL-12 and the anti-inflammatory cytokine IL-10 are known to play major roles. Here, we show that in vitro or in vivo stimulation with flagellin, the TLR5 ligand, does not result in IL-10 production. Furthermore, flagellin inhibits IL-10 production by other specific TLR ligands at the protein and mRNA levels while increasing IL-12p70 production. Several studies have linked the activation of extracellular signal-regulated kinases with IL-10 induction by TLR. We have observed that LPS-induced extracellular signal-regulated kinase activation was significantly decreased in flagellin-treated macrophages, suggesting that this pathway might play a role in the inhibition of IL-10 production observed in flagellin-treated macrophages. Flagellin-mediated IL-10 inhibition was not observed in cells that do not express TLR5, supporting that this effect is indeed TLR5-dependent. This study provides a new insight into the role of flagellin recognition by TLR5 in shaping the immune response elicited by flagellated microorganisms.
Vicente-Suarez
Ildefonso
I
Division of Immunology, Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center & Research Institute, University of South Florida, Tampa, FL 33612, USA.
Takahashi
Yoshinori
Y
Cheng
Fengdong
F
Horna
Pedro
P
Wang
Hong W
HW
Wang
Hong-Gang
HG
Sotomayor
Eduardo M
EM
D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005408:Flagellin / Q000378:metabolism*; D015870:Gene Expression; D007249:Inflammation / Q000378:metabolism*; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051198:Toll-Like Receptor 5 / Q000378:metabolism*
D012333:RNA, Messenger; D051198:Toll-Like Receptor 5; D005408:Flagellin; D016753:Interleukin-10; D018664:Interleukin-12; D048049:Extracellular Signal-Regulated MAP Kinases