Immunity to Tuberculosis and Novel Therapeutic Strategies

Both innate and adaptive immunity is involved in the cellular immune response against Mycobacterium tuberculosis (Mtb). Alveolar macrophages (Mθ) actively participate to the engulfment and killing of Mtb, while dendritic cells (DCs) act as antigen presenting cells. Also, neutrophils and natural killer cells protect the host against Mtb. Adaptive immunity is based on the DC-mediated activation of Th1 cells, that produce interferon-γ and enhance the microbicidal activity of Mθ. Moreover, T regulatory (Treg) and Th17 cells seem to play antithetic roles in which the former are able to exert anti-inflammatory functions and the latter contribute to the exacerbation of inflammation. Despite such a defensive armamentarium, Mtb has been shown to escape from the host immunity adopting different strategies. Intradermal vaccination with Bacille Calmette Guerin (BCG) has been replaced by the intranasal route using viral-vectored tuberculosis (TB) vaccines which better boost BCG immunization. Also, Mtb filtrate proteins, mucosal adjuvants and IgA monoclonal antibodies have been experimented in the immunotherapy against TB. Vitamin D has been shown to be protective in the course of TB in view of its receptors present on Mθ and Treg cells. Finally, polyphenols have been demonstrated to restore Mtb mediated depression of Mθ function as well as to directly act on Mtb, thus arresting its growth. From our own studies with red grape polyphenols, it emerges that these compounds may support Th1 responses, especially in elderly patients, also exerting Treg cell-mediated anti-inflammatory activity via IL-10 release. Therefore, polyphenol supplementation may contribute to reinforce anti-Mtb defences and mitigate excessive inflammation