Subsequent investigations have suggested that vitamin D, via cathelicidin, can also induce autophagy One study has shown that vitamin D3 specifically induces autophagy in human monocytes and macrophages via cathelicidin [49], and that cathelicidin comes into direct contact with mycobacteria within the autophagosome. Vitamin D supplementation in patients deficient in vitamin D did not, however, increase circulating cathelicidin [50]. None the less, localized increases of this anti-microbial peptide may be achievable in the granuloma – which might not be detectable by peripheral sampling. Further studies are needed to

assess the true benefits, if any, of vitamin D in the immune response to tuberculosis and what role Compound Library cost autophagy might play in this. Autophagy assists with antigen processing of intracellular and extracellular material for major histocompatibility complex (MHC) class I and class II presentation, and has also been shown to Roxadustat order be important for efficient cross-presentation to CD8+ T lymphocytes. Autophagosomes containing pathogens, including mycobacteria, converge with endosomes and thus deliver antigens for loading in MHC class II compartments. Autophagy can also deliver endogenous antigens to the MHC II pathway [51] enhancing presentation to CD4+ T cells [52–56]. These studies showed a direct association of autophagy

with enhanced delivery of endogenous proteins to the MHC class II pathway and suggest that autophagy is a mechanism by which the peptide repertoire presented by MHC class II molecules may be extended from exogenous to endogenous antigens.

Methisazone There is evidence that autophagy-associated proteins, including LC3, gain access to MHC II compartments [57] and coupling of antigens to Atg8/LC3 enhanced their presentation on MHC class II [58]. Moreover, the induction (with rapamycin or starvation) or suppression (with 3-MA or RNAi knock-down) of autophagy have been shown to have direct effects on MHC II-peptide presentation [59,60]. In vivo, autophagy has also been shown to be important for MHC class II presentation of self-proteins during central tolerance induction [61]. In the context of mycobacteria, autophagy also enhances MHC class II presentation. Vaccination with rapamycin-treated DC enhanced MHC class II presentation of Ag85B and was associated with the induction of potent protective CD4+ responses in mice [62]. Autophagy may also contribute to the generation of MHC class I-restricted responses. English et al. demonstrated that autophagy contributed to processing of herpes simplex virus-1 antigens for MHC class I presentation [63]. Autophagy may also influence antigen presentation to CD8+ T cells via degradation of the MHC class I molecules themselves [64]. Autophagy induction resulted in reduced MHC class I surface expression, consistent with the presence of MHC I in autophagosomes, but this was reversed by IFN-γ.