Host factors subverted by Mycobacterium tuberculosis: Potential targets for host directed therapy.

Abstract

Introduction: Despite new approaches in the diagnosis and treatment of tuberculosis (TB), it continues to be a major health burden. Several immunotherapies that potentiate the immune response have come up as adjuncts to drug therapies against drug resistant TB strains; however, there needs to be an urgent appraisal of host specific drug targets for improving their clinical management and to curtail disease progression. Presently, various host directed therapies (HDTs) exist (repurposed drugs, nutraceuticals, monoclonal antibodies and immunomodulatory agents), but these mostly address molecules that combat disease progression.

Areas covered: The current review discusses major Mycobacterium tuberculosis (M. tuberculosis) survival paradigms inside the host and presents a plethora of host targets subverted by M. tuberculosis which can be further explored for future HDTs. The host factors unique to M. tuberculosis infection (in humans) have also been identified through an in-silico interaction mapping.

Expert opinion: HDTs could become the next-generation adjunct therapies in order to counter antimicrobial resistance and virulence, as well as to reduce the duration of existing TB treatments. However, current scientific efforts are largely directed toward combatants rather than host molecules co-opted by M. tuberculosis for its survival. This might drive the immune system to a hyper-inflammatory condition; therefore, we emphasize that host factors subverted by M. tuberculosis, and their subsequent neutralization, must be considered for development of better HDTs.