Silencing SOCS1 in dendritic cells promote survival of mice with systemic Candida albicans infection via inducing Th1-cell differentiation

Abstract

Enhancing the immunity conferred by dendritic cells (DCs) to fungal infection represents a promising strategy in the number of immunocompromised individuals. In a previous study, we demonstrated that suppressor of cytokine signaling 1 (SOCS1) silencing can promote the maturation of DCs and induce an immune response against Candida albicans (C. albicans) in vitro. Herein, the effectiveness of SOCS1 suppression administered by SOCS1-siRNA-treated DCs is further evaluated in systemic candidiasis mouse model. The SOCS1-silenced DCs increase mouse survival and significantly decrease fungal colonization in the kidneys. We confirm that the serum IFN-γ levels in SOCS1-siRNA-treated mice are higher than in all other infected groups at the early stages of infection, which correlates with a higher differentiation of IFN-γ+CD4+ T cells (Th1) in the spleen. Meanwhile, the differentiation of IL-4-producing CD4+ T (Th2) or IL-17-producing CD4+ T cells (Th17 cells) remain unaffected under the same treatment, suggesting that SOCS1-silenced DCs significantly affect the IFN-γ-producing CD4+ T cells (Th1). However, at the late stages of infection when the differentiation of Th1, Th2 and Th17 cells decreases in SOCS1-silenced-DCs-treated mice, all the serum cytokines (IFN-γ, IL-4 and IL-17) are also reduced. In summary, treatment of mice with SOCS1-silenced DCs can protect mice from systemic infection during the early stages and thereby increase overall survival. We conclude that the increase in Th1 response in early stages avoids the cascade inflammatory response in later stages that is known to place such a large fungal load on the kidneys and cause subsequent death.