Host-directed therapy for tuberculosis

Abstract

Current TB treatment regimens are hindered by drug resistance, numerous adverse effects, and long treatment durations, highlighting the need for 'me-better' treatment regimens. Host-directed therapy (HDT) has gained recognition as a promising approach in TB treatment. It allows the repurposing of existing drugs approved for other conditions and aims to enhance the effectiveness of existing anti-TB therapies, minimize drug resistance, decrease treatment duration, and adverse effects. By modulating the host immune response, HDT ameliorates immunopathological damage and improves overall outcomes by promoting autophagy, antimicrobial peptide production, and other mechanisms. It holds promise for addressing the challenges posed by multiple and extensively drug-resistant Mycobacterium tuberculosis strains, which are increasingly difficult to treat using conventional therapies. This article reviews various HDT candidates, including repurposed drugs, explores their underlying mechanisms such as autophagy promotion and inflammation reduction, while emphasizing their potential to improve TB treatment outcomes and outlining future research directions.

Keywords: Mycobacterium tuberculosis; Host response; Host-directed therapy; Infectious diseases; Tuberculosis.

Fig. 1

Main current HDTs used in tuberculosis

Fig. 2

Schematic representation of the correlation between autophagy induction and the anti-tuberculosis activity of indicated cytokines and pharmacological agents

Fig. 3

Statins and M.tb infection exhibit opposing effects on AMPK, mTORC1, and autophagy. Statins suppress mTORC1 activity while activating AMPK, both of which cause enhanced nuclear translocation of TFEB, resulting in the expression of autophagy-related genes. M.tb produces opposite effects by activating mTORC1 and blocking AMPK, which prevents nuclear translocation of TFEB and inhibits autophagy

Fig. 4

The structure and main composition of granuloma and related drugs