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Silenced suppressor of cytokine signaling 1 (SOCS1) enhances the maturation and antifungal immunity of dendritic cells in response to Candida albicans in vitro.

Abstract：

:Dendritic cells (DCs) are known to play an important role in initiating and orchestrating antimicrobial immunity. Given the fact that candidiasis appears often in immunocompromised patients, it seems plausible that DCs hold the key to new antifungal strategies. One possibility to enhance the potency of DC-based immunotherapy is to silence the negative immunoregulatory pathways through the ablation suppressor of cytokine signaling suppressor 1 (SOCS1). Here, we deliver small interfering RNA (siRNA) against SOCS1 into murine bone marrow DCs, and as a consequence, we investigate the maturation/action of DCs and the subsequent T cell response after exposure to C. albicans. Our results show that the maturation of DCs (i.e., expressions of CD80, CD40, CD86, and MHC II) are significantly increased in the silenced SOCS1 treatment group after exposure to C. albicans. As a result, suppression of the SOCS1 promotes the greatest expression of IFN-γ and IL-12, and reduces IL-4 secretions, which induce CD4(+) cell Th1 differentiation but inactivate Th2 cell development. The responses of IL-6 and TNF-β consist of up-regulation in the presence of C. albicans, but this is not specific to SOCS1 silencing, suggesting that these cytokines are not regulated by the SOCS1 gene in fungal infections. We find Th17 differentiation is unchanged regardless of SOCS1 inhibition. The increase in phagocytosis and killing of C. albicans in SOCS1 gene-treated DCs indicate a role for this cytokine suppressor in innate immunity as well. In conclusion, our findings support the view that SOCS1 protein is a critical inhibitory molecule for controlling cytokine response and antigen presentation by DCs, thereby regulating the magnitude of innate and adaptive immunities by generating IFN-γ-production T cells (Th1)--but not Th17--from naïve CD4(+) T cells. Our study demonstrates that SOCS1 siRNA can serve as a useful vehicle to modulate the function of DCs against C. albicans infection.

journal_name

Immunol Res

journal_title

Immunologic research

authors

Shi D,Li D,Yin Q,Qiu Y,Yan H,Shen Y,Lu G,Liu W

doi

10.1007/s12026-014-8562-8

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

206-18

issue

eissn

0257-277X

issn

1559-0755

journal_volume

pub_type

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Silenced suppressor of cytokine signaling 1 (SOCS1) enhances the maturation and antifungal immunity of dendritic cells in response to Candida albicans in vitro.