TLR4 and Toll-IL-1 Receptor Domain-Containing Adapter-Inducing IFN-β, but Not MyD88, Regulate<i>Escherichia coli</i>-Induced Dendritic Cell Maturation and Apoptosis In Vivo

Trez, Carl De; Pajak, Bernard; Brait, Maryse; Glaichenhaus, Nicolas; Urbain, Jacques; Moser, Muriel; Lauvau, Grégoire; Muraille, Eric

doi:10.4049/jimmunol.175.2.839

Cited by 76 publications

(64 citation statements)

References 36 publications

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“…This result was confirmed when in vivo splenic DC maturation was impaired in MyD88KO mice that received HKBA but not in TLR2 KO or TLR9 KO animals. Conversely, E. coli LPS could induce functional maturation of MyD88-deficient DC as previously reported (34). The inhibition of Brucella-induced DC maturation in MyD88-deficient mice argues in favor of a critical role for MyD88 in the detection of B. abortus by DC.…”

Section: Discussionsupporting

confidence: 80%

Central Role of MyD88-Dependent Dendritic Cell Maturation and Proinflammatory Cytokine Production to Control Brucella abortus Infection

Macedo¹,

Magnani²,

Carvalho³

et al. 2008

The Journal of Immunology

144

159

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Brucella abortus is a facultative intracellular bacterium that infects humans and domestic animals. The enhanced susceptibility to virulent B. abortus observed in MyD88 knockout (KO) mice led us to investigate the mechanisms involved in MyD88-dependent immune responses. First, we defined the role of MyD88 in dendritic cell (DC) maturation. In vitro as well as in vivo, B. abortus-exposed MyD88 KO DCs displayed a significant impairment on maturation as observed by expression of CD40, CD86, and MHC class II on CD11c+ cells. In addition, IL-12 and TNF-α production was totally abrogated in MyD88 KO DCs and macrophages. Furthermore, B. abortus-induced IL-12 production was found to be dependent on TLR2 in DC, but independent on TLR2 and TLR4 in macrophages. Additionally, we investigated the role of exogenous IL-12 and TNF-α administration on MyD88 KO control of B. abortus infection. Importantly, IL-12, but not TNF-α, was able to partially rescue host susceptibility in MyD88 KO-infected animals. Furthermore, we demonstrated the role played by TLR9 during virulent B. abortus infection. TLR9 KO-infected mice showed 1 log Brucella CFU higher than wild-type mice. Macrophages and DC from TLR9 KO mice showed reduced IL-12 and unaltered TNF-α production when these cells were stimulated with Brucella. Together, these results suggest that susceptibility of MyD88 KO mice to B. abortus is due to impaired DC maturation and lack of IL-12 synthesis. Additionally, DC activation during Brucella infection plays an important regulatory role by stimulating and programming T cells to produce IFN-γ.

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Section: Discussionsupporting

confidence: 80%

Central Role of MyD88-Dependent Dendritic Cell Maturation and Proinflammatory Cytokine Production to Control Brucella abortus Infection

Macedo¹,

Magnani²,

Carvalho³

et al. 2008

The Journal of Immunology

144

159

View full text Add to dashboard Cite

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“…TRIF-mediated signaling by TLR3 and -4 in various cell types induces an apoptotic response that depends on the production of endogenous type I IFN (6,8,(41)(42)(43)(44). In the case of antigen-presenting cells such as DCs, TLR3 and -4 signaling may induce apoptosis before or after pathogen-derived peptides have been presented at DC surface, and this process may be critical for controlling the delicate balance between antigen cross-presentation and DC maturation.…”

Section: Discussionmentioning

confidence: 99%

Cell proliferation and survival induced by Toll-like receptors is antagonized by type I IFNs

Hasan

Caux

Perrot

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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TRIF is an adaptor protein associated with the signaling by Toll-like receptor (TLR)3 and TLR4 for the induction of type I IFNs. Here, we demonstrate a mechanism by which TLR signaling controls cell proliferation and survival. We show that TLR3 and TLR4 can induce cell cycle entry via TRIF, which targets the cell cycle inhibitor p27 kip1 for relocalization, phosphorylation by cyclin/cdk complexes, and proteasome degradation. These events are antagonized by type I IFN induced by the TRIF pathway. Furthermore, in human dendritic cells treated with TLR3, TLR4, or TLR5 ligands, we demonstrate that IFN signaling modulates p27 kip1 degradation and apoptosis, identifying an immunoregulatory ''switching'' function of type I IFNs. These findings reveal a previously uncharacterized function of TLR signaling in cell proliferation and survival.cell cycle ͉ p27

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“…4). AICAR also was assayed for the ability to induce DC migration in vivo, as described previously (42)(43)(44). Most DCs, identified by the CD11c marker, were found in the splenic marginal zones and around the central arterioles of control, untreated animals (Fig.…”

Section: Lack Of Inflammatory Response To Aicar Administrationmentioning

confidence: 99%

Metabolic Stress Boosts Humoral Responses In Vivo Independently of Inflammasome and Inflammatory Reaction

Andris

Denanglaire

Baus

et al. 2011

The Journal of Immunology

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Adjuvant formulations boost humoral responses by acting through several, yet incompletely elucidated pathways. In this study, we show that oligomycin or 5-aminoimidazole-4-carboxamide-1-β-d-ribonucleoside (AICAR) enhances Ab production when coinjected with T cell-dependent Ags. Oligomycin and AICAR lead to intracellular ATP reduction, suggesting that metabolic stress could be sensed by immune cells and leads to increased humoral responses. AICAR promotes IL-4 and IL-21 by naive Th cells but does not affect dendritic cell activation/maturation in vitro or in vivo. Accordingly, the adjuvant effect of AICAR or oligomycin does not require MyD88 or caspase-1 expression in vivo. Because AICAR is well tolerated in humans, this compound could represent a novel and safe adjuvant promoting humoral responses in vivo with a minimal reactogenicity.

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TLR4 and Toll-IL-1 Receptor Domain-Containing Adapter-Inducing IFN-β, but Not MyD88, RegulateEscherichia coli-Induced Dendritic Cell Maturation and Apoptosis In Vivo

Cited by 76 publications

References 36 publications

Central Role of MyD88-Dependent Dendritic Cell Maturation and Proinflammatory Cytokine Production to Control Brucella abortus Infection

Central Role of MyD88-Dependent Dendritic Cell Maturation and Proinflammatory Cytokine Production to Control Brucella abortus Infection

Cell proliferation and survival induced by Toll-like receptors is antagonized by type I IFNs

Metabolic Stress Boosts Humoral Responses In Vivo Independently of Inflammasome and Inflammatory Reaction

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