Earle's balanced salts solution and rapamycin differentially regulate the Bacillus Calmette-Guerin-induced maturation of human dendritic cells

Abstract

Autophagy has been shown to enhance the efficacy of the Bacillus Calmette-Guérin (BCG) vaccine by increasing the peptide presentation of dendritic cells (DCs). Earle's balanced salts solution (EBSS) is a saline solution with physiological pH which is often used to induce autophagy, while rapamycin is a pharmacological reagent used for autophagy induction. In the present study, we studied the effect of EBSS and rapamycin on the maturation of DCs infected with BCG. The phenotype and function of the DCs were assessed by measuring the expression of CD86 and HLA-DR and the secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-12p40. Autophagy was evaluated by the level of LC3-II, a molecular marker for autophagy. Following the stimulation of autophagy by EBSS, the DCs that matured in the presence of BCG showed enhanced CD86 and HLA-DR expression and increased IL-12p40 and TNF-α production. In contrast, following the stimulation of autophagy by rapamycin, the DCs that matured in the presence of BCG showed decreased expression of CD86 and reduced production of IL-12p40 and TNF-α. These results demonstrated that EBSS and rapamycin differentially regulate the BCG-induced maturation of human DCs. This suggests that EBSS could contribute to an enhanced adaptive immune response against Mycobacterium tuberculosis, whereas rapamycin, as an immune depressor, may decrease the adaptive immune response against M. tuberculosis.