The shaping of adaptive immune responses to soluble proteins by TLR agonists: A role for IFN alpha/beta

V. Durand, Simon Yuk Chun Wong, D. F. Tough, A. Le Bon

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Toll-like receptors (TLR) are believed to play a major role in the recognition of invading organisms, although their ability to shape immune responses is not completely understood. Our aim was to investigate in vivo the effect of different TLR stimuli on the generation of antibody responses and the induction of CD8(+) T-cell cross-priming after immunization with soluble protein antigens. While all TLR agonists tested elicited the production of immunomodulatory cytokines, marked differences were observed in their ability to stimulate antigen-specific immune responses. Zymosan, poly(I:C) and CpG DNA, which signal through TLR2/6, 3 and 9, respectively, were found to strongly induce the production of IgG2a antibodies, whereas R-848 (TLR7) and LPS (TLR4) did so much more weakly. In contrast, LPS, poly(I:C) and CpG DNA, but not zymosan, induced functional CD8(+) T-cell responses against OVA; peptidoglycan (TLR2/?) and R-848 were also ineffective in stimulating cross-priming. Experiments using IFN-alpha/betaR-deficient mice showed that the induction of cross-priming by LPS and poly(I:C) was abrogated in the absence of IFN-alpha/beta signalling, and induction by CpG DNA was greatly reduced. Overall, our results identify LPS as another TLR agonist that is able to generate functional cross-priming against a soluble protein antigen. In addition, our results demonstrate that the ability of TLR stimuli to initiate CD8(+) T-cell responses against soluble protein antigens is largely dependent on the IFN-alpha/beta signalling pathway.

Original languageEnglish
Pages (from-to)596-602
Number of pages6
JournalImmunology and Cell Biology
Volume82
DOIs
Publication statusPublished - 2004

Keywords

  • cross-priming
  • cytokines
  • interferon-alpha/beta
  • IgG2a
  • pro-inflammatory
  • toll-like receptors
  • TOLL-LIKE RECEPTORS
  • ACTIVATES DENDRITIC CELLS
  • HUMORAL IMMUNITY
  • I INTERFERON
  • VIVO

Cite this

The shaping of adaptive immune responses to soluble proteins by TLR agonists: A role for IFN alpha/beta. / Durand, V.; Wong, Simon Yuk Chun; Tough, D. F.; Le Bon, A.

In: Immunology and Cell Biology, Vol. 82, 2004, p. 596-602.

Research output: Contribution to journalArticle

Durand, V. ; Wong, Simon Yuk Chun ; Tough, D. F. ; Le Bon, A. / The shaping of adaptive immune responses to soluble proteins by TLR agonists: A role for IFN alpha/beta. In: Immunology and Cell Biology. 2004 ; Vol. 82. pp. 596-602.
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