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Toll-like receptor ligands induce expression of the costimulatory molecule CD155 on antigen-presenting cells.

ABSTRACT: Genotoxic stress and RAS induce the expression of CD155, a ligand for the immune receptors DNAM-1, CD96 and TIGIT. Here we show that antigen-presenting cells upregulate CD155 expression in response to Toll-like receptor activation. Induction of CD155 by Toll-like receptors depended on MYD88, TRIF and NF-κB. In addition, IRF3, but not IRF7, modulated CD155 upregulation in response to TLR3 signals. Immunization of CD155-deficient mice with OVA and the TLR9 agonist CpG resulted in increased OVA-specific IgG2a/c titers when compared to wild type mice. Splenocytes of immunized CD155-deficient mice secreted lower levels of IL-4 and fewer IL-4 and GATA-3 expressing CD4(+) T cells were present in the spleen of Cd155(-/-) mice. Our data suggest that CD155 regulates T(h)2 differentiation. Targeting of CD155 in immunization protocols using peptides may represent a promising new approach to boost protective humoral immunity in viral vaccines.

SUBMITTER: Kamran N

PROVIDER: S-EPMC3547938 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Toll-like receptor ligands induce expression of the costimulatory molecule CD155 on antigen-presenting cells.

Kamran Neha N Takai Yoshimi Y Miyoshi Jun J Biswas Subhra K SK Wong Justin S B JS Gasser Stephan S

PloS one 20130117 1

Genotoxic stress and RAS induce the expression of CD155, a ligand for the immune receptors DNAM-1, CD96 and TIGIT. Here we show that antigen-presenting cells upregulate CD155 expression in response to Toll-like receptor activation. Induction of CD155 by Toll-like receptors depended on MYD88, TRIF and NF-κB. In addition, IRF3, but not IRF7, modulated CD155 upregulation in response to TLR3 signals. Immunization of CD155-deficient mice with OVA and the TLR9 agonist CpG resulted in increased OVA-spe ...[more]

PMID: 23349877

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Project description:Lactoferrin (LF), a key element in mammalian immune system, plays pivotal roles in host defence against infection and excessive inflammation. Its protective effects range from direct antimicrobial activities against a large panel of microbes, including bacteria, viruses, fungi and parasites, to antinflammatory and anticancer activities. In this study, we show that monocyte-derived dendritic cells (MD-DCs) generated in the presence of bovine LF (bLF) fail to undergo activation by up-modulating CD83, co-stimulatory and major histocompatibility complex molecules, and cytokine/chemokine secretion. Moreover, these cells are weak activators of T cell proliferation and retain antigen uptake activity. Consistent with an impaired maturation, bLF-MD-DC primed T lymphocytes exhibit a functional unresponsiveness characterized by reduced expression of CD154 and impaired expression of IFN-γ and IL-2. The observed imunosuppressive effects correlate with an increased expression of molecules with negative regulatory functions (i.e. immunoglobulin-like transcript 3 and programmed death ligand 1), indoleamine 2,3-dioxygenase, and suppressor of cytokine signaling-3. Interestingly, bLF-MD-DCs produce IL-6 and exhibit constitutive signal transducer and activator of transcription 3 activation. Conversely, bLF exposure of already differentiated MD-DCs completely fails to induce IL-6, and partially inhibits Toll-like receptor (TLR) agonist-induced activation. Cell-specific differences in bLF internalization likely account for the distinct response elicited by bLF in monocytes versus immature DCs, providing a mechanistic base for its multiple effects. These results indicate that bLF exerts a potent anti-inflammatory activity by skewing monocyte differentiation into DCs with impaired capacity to undergo activation and to promote Th1 responses. Overall, these bLF-mediated effects may represent a strategy to block excessive DC activation upon TLR-induced inflammation, adding further evidence for a critical role of bLF in directing host immune function.

Dataset Information

Toll-like receptor ligands induce expression of the costimulatory molecule CD155 on antigen-presenting cells.

Publications

Toll-like receptor ligands induce expression of the costimulatory molecule CD155 on antigen-presenting cells.

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