Autophagy promotes BCG-induced maturation of human dendritic cells

Abstract

Dendritic cells (DCs) are important for the initiation of the adaptive immune response against Mycobacterium tuberculosis. Autophagy is an innate and adaptive defense mechanism and important for the control of M. tuberculosis. However, the role of autophagy in the adaptive immune response against M. tuberculosis remains to be determined. In the present study, we studied the effects of autophagy on the maturation of DCs infected with Bacillus CalmetteGuérin (BCG). The phenotype and function of the DCs were assessed by measuring the expression of CD86 and HLA-DR and the secretion of IL-10 and IL-6. Autophagy was evaluated by the change in LC3II, a molecular marker for autophagy. Following stimulation of autophagy, DCs that were matured in the presence of BCG showed enhanced expression of CD86 and HLA-DR and increased IL-6 production. The expression of LC3II was increased after the stimulation of autophagy. These results demonstrated that autophagy might result in the increased maturation of BCG-infected DCs, suggesting that autophagy could contribute to an enhanced adaptive immune response against M. tuberculosis.

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

“…In our previous study, we showed that Earle's balanced salts solution (EBSS), a saline solution with physiological pH which is often used to induce autophagy, enhances BCG-induced DC maturation via the up-regulation of CD86, HLA-DR, and IL-6 [6]. In the present study, we found that EBSS and rapamycin differentially regulated the maturation of human DCs.…”

“…6). Our previous data demonstrated that the LC3-II level was increased when THP-1 cells were treated with different ratios of EBSS, with 12.5% and 25% EBSS enhancing the LC3-II level in BCG-infected THP-1 cells [6]. Collectively, these results indicate that rapamycin and EBSS enhance the activity of autophagy in BCG-infected THP-1 cells.…”

“…In our previous studies, we first infected the DCs with BCG and then treated them with EBSS [6]. In the present study, we first treated uninfected DCs with EBSS and then infected them with BCG.…”

Burkholderia cenocepacia J2315 escapes to the cytosol and actively subverts autophagy in human macrophages

“…As such, the level of p62 should decrease with increased autophagic flux, while a block in autophagosome maturation will lead to p62 accumulation (Kuma et al , 2007). Treatment of THP-1 cells with chloroquine (CQ), which is known to block autophagosomal maturation (Chiu et al , 2009, Min et al , 2009), led to the expected increase in both the conversion of LC3B-I to LC3B-II, and accumulation of p62 (Fig. 4B).…”

Autophagy Controls BCG-Induced Trained Immunity and the Response to Intravesical BCG Therapy for Bladder Cancer

“…Transcriptomic assessment of these monocytes by microarrays and pathway analysis revealed specific clusters of genes significantly induced by β-glucan training with an intriguing signal found in the ubiquitin-related proteins and associated catabolic processes (Figure 1a). Since ubiquitination plays an important role in autophagy [8], a process that has previously been shown to improve intracellular processing of BCG [9], [10], we examined the role of autophagy in the induction of trained immunity.…”