Dataset Information

Dectin-1/TLR2 and NOD2 agonists render dendritic cells susceptible to infection by X4-using HIV-1 and promote cis-infection of CD4(+) T cells.

ABSTRACT: HIV-1 pathogenesis is intimately linked with microbial infections and innate immunity during all stages of the disease. While the impact of microbial-derived products in transmission of R5-using virus to CD4(+) T cells by dendritic cells (DCs) has been addressed before, very limited data are available on the effect of such compounds on DC-mediated dissemination of X4-tropic variant. Here, we provide evidence that treatment of DCs with dectin-1/TLR2 and NOD2 ligands increases cis-infection of autologous CD4(+) T cells by X4-using virus. This phenomenon is most likely associated with an enhanced permissiveness of DCs to productive infection with X4 virus, which is linked to increased surface expression of CXCR4 and the acquisition of a maturation profile by DCs. The ensuing DC maturation enhances susceptibility of CD4(+) T cells to productive infection with HIV-1. This study highlights the crucial role of DCs at different stages of HIV-1 infection and particularly in spreading of viral strains displaying a X4 phenotype.

SUBMITTER: Cote SC

PROVIDER: S-EPMC3699635 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Dectin-1/TLR2 and NOD2 agonists render dendritic cells susceptible to infection by X4-using HIV-1 and promote cis-infection of CD4(+) T cells.

Côté Sandra C SC Plante Audrey A Tardif Mélanie R MR Tremblay Michel J MJ

PloS one 20130702 7

HIV-1 pathogenesis is intimately linked with microbial infections and innate immunity during all stages of the disease. While the impact of microbial-derived products in transmission of R5-using virus to CD4(+) T cells by dendritic cells (DCs) has been addressed before, very limited data are available on the effect of such compounds on DC-mediated dissemination of X4-tropic variant. Here, we provide evidence that treatment of DCs with dectin-1/TLR2 and NOD2 ligands increases cis-infection of aut ...[more]

PMID: 23844079

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Project description:Leptospira interrogans are pathogenic spirochetes responsible for leptospirosis, a worldwide reemerging zoonosis. Many Leptospira serovars have been described, and prophylaxis using inactivated bacteria provides only short-term serovar-specific protection. Therefore, alternative approaches to limit severe leptospirosis in humans and morbidity in cattle would be welcome. Innate immune cells, including macrophages, play a key role in fighting infection and pathogen clearance. Recently, it has been shown that functional reprograming of innate immune cells through the activation of pattern recognition receptors leads to enhanced nonspecific antimicrobial responses upon a subsequent microbial encounter. This mechanism is known as trained immunity or innate immune memory. We have previously shown that oral treatment with Lactobacillus plantarum confers a beneficial effect against acute leptospirosis. Here, using a macrophage depletion protocol and live imaging in mice, we established the role of peritoneal macrophages in limiting the initial dissemination of leptospires. We further showed that intraperitoneal priming of mice with CL429, a TLR2 and NOD2 agonist known to mimic the modulatory effect of Lactobacillus, alleviated acute leptospiral infection. The CL429 treatment was characterized as a training effect since i.) it was linked to peritoneal macrophages that produced ex vivo more pro-inflammatory cytokines and chemokines against 3 different pathogenic serovars of Leptospira, independently of the presence of B and T cells, ii.) it had systemic effects on splenic cells and bone marrow derived macrophages, and iii.) it was sustained for 3 months. Importantly, trained macrophages produced more nitric oxide, a potent antimicrobial compound, which has not been previously linked to trained immunity. Accordingly, trained macrophages better restrict leptospiral survival. Finally, we could use CL429 to train ex vivo human monocytes that produced more cytokines upon leptospiral stimulation. In conclusion, host-directed treatment using a TLR2/NOD2 agonist could be envisioned as a novel prophylactic strategy against acute leptospirosis.

Dataset Information

Dectin-1/TLR2 and NOD2 agonists render dendritic cells susceptible to infection by X4-using HIV-1 and promote cis-infection of CD4(+) T cells.

Publications

Dectin-1/TLR2 and NOD2 agonists render dendritic cells susceptible to infection by X4-using HIV-1 and promote cis-infection of CD4(+) T cells.

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