Immune defense and immune evasion in Mycobacterium tuberculosis Infection: Inspirations and challenges for host directed therapy

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global public health issue, despite improvements in socioeconomic conditions and widespread use of antibiotics. Host immune defense against Mtb infection involve various cells like macrophages, dendritic cells, natural killer cells and T cell subsets, which play distinct roles. By inhibiting phagosome maturation, modulating reactive oxygen and nitrogen species production, regulating host cell death pathway, as well as suppressing antigen presentation and T cell immune responses, the immune escape help Mtb to survive and replicate in macrophages, which ultimately contributes to the development of latent or active TB. While traditional TB treatment strategy suffers challenges like low efficacy, long treatment durations and side effects, the emergence of drug-resistant TB (DR-TB) and multidrug-resistant TB (MDR-TB), which further highlight the therapeutic challenges due to the low cure rate. Host Directed Therapy (HDT) is an emerging supplementary approach to TB treatment, which leverages insights into how host immune cells defend Mtb infection, as well as how pathogens manipulate host immune defense mechanisms. HDT is an approach for treating TB that appropriately modulates host immune responses, which aims to enhance the antimicrobial activity of the host. In this review, we summarized the host immune defense mechanisms, as well as analyzed how Mtb evades host immunological killings, thus potentially providing new insights into the host-pathogen interactions during Mtb infection and TB development. Furthermore, we reviewed recent advances in exploring HDT strategies for effective anti-TB interventions, which may highlight more effective therapeutics to fight against TB.