当前位置： SCI文献检索 > JOURNAL OF LEUKOCYTE BIOLOGY期刊下所有文献 > Cross-talk between toll-like receptors 5 and 9 on activation of human immune responses.

Cross-talk between toll-like receptors 5 and 9 on activation of human immune responses.

Abstract：

:The recognition of pathogen-associated molecular patterns by TLRs triggers the activation of innate and adaptive immune responses. Flagellin, the agonist of TLR5, is expressed by prokaryotes and eukaryotes, and DNA sequences containing unmethylated CpG dinucleotides, agonists of TLR9, are present essentially in prokaryotes. To test the potential modulating effects of simultaneous activation of different TLRs on the immune response, we compared the outcomes in different immune cell compartments induced by triggering TLR5 and TLR9 individually and in combination. PBMCs, monocytes, and monocyte-derived DC (MoDC) secreted high levels of IL-10 in response to flagellin, whereas oligodeoxynucleotides (ODN) containing the CpG sequence (CpG-ODN), synthetic ligands of TLR9, did not induce IL-10 secretion in any of the three cell types but synergized with flagellin in this induction. In contrast, PBMC production of IFN-alpha induced by CpG-ODN was strongly inhibited by flagellin. Conversely, CpG-ODN did not enhance the up-regulation of activation markers in MoDC induced to mature in the presence of flagellin. Flagellin-matured, but not CpG-ODN-matured, MoDC stimulated the expansion of allogeneic CD4+CD25+ T cells, and the extent of expansion induced by MoDC, matured in the presence of flagellin and CpG-ODN, was similar to that induced by flagellin-matured MoDC. Moreover, flagellin and CpG-ODN differentially affected NK-mediated cytotoxicity, and flagellin completely abrogated the NK-mediated immune response induced by CpG-ODN stimulation. Together, these results suggest that flagellin inhibits the TLR9-induced cell activation and cytokine production, which favor Th1-type immune responses, possibly because the signals evoked by flagellin to indicate the presence of extracellular pathogens must favor a Th2-polarized response. Thus, TLR5 and TLR9, alerted by the presence of microorganisms, influence each other to mount the more efficient and appropriate immune response to contain the infection of a specific pathogen.

journal_name

J Leukoc Biol

journal_title

Journal of leukocyte biology

authors

Merlo A,Calcaterra C,Mènard S,Balsari A

doi

10.1189/jlb.0207100

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

509-18

issue

eissn

0741-5400

issn

1938-3673

pii

jlb.0207100

journal_volume

pub_type

杂志文章

在线工具

Cross-talk between toll-like receptors 5 and 9 on activation of human immune responses.