Host-mycobacteria conflict: Immune responses of the host vs. the mycobacteria TLR2 and TLR4 ligands and concomitant host-directed therapy

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the most grievous infectious diseases with long-term morbidity and unpredicted mortality rates globally. Thus, understanding the host-pathogen interactions to develop potential drugs is the most focused area of research. Mtb has many antigens communicating with host cells via various pattern recognition receptors (PRRs). From which, toll-like receptors-2 and 4 (TLR2 and 4) are two major PRRs that provide the primary immune response to Mtb infection of the respiratory tract. As a result, the TLR-mycobacterium antigen interaction triggers a variety of crucial innate immune signalling mechanisms such as phagosome maturation, oxidative stress, elicitation of cell deaths, production of proinflammatory cytokines, and eventually associates with the adaptive immune response to establish infection. Despite the extensive investigations on TLR2 and 4 Mtb ligands that have a significant role in the immune defence system, there are still many unsolved concerns driving researchers to explore the obscures. This review focuses on the host immune modulation due to Mtb-TLR2 and 4 ligand interaction. Subsequently, the host TLR2 and 4 immune signals in cooperation with other PRRs and successive cytokine expressions are discussed. Also highlighted are some recent findings on host-directed therapy related to TLRs that aid in developing novel immunotherapeutic prospects for the better control of Mtb infection. © 2022 Elsevier GmbH