Mycobacterium tuberculosis host cell interaction: Role of latency associated protein Acr-1 in differential modulation of macrophages

Abstract

Mycobacterium tuberculosis (M.tb) contrives intracellular abode as a strategy to combat antibody onslaught. Additionally, to thrive against hostile ambiance inside host macrophages, the pathogen inhibits phago-lysosomal fusion. Finally, to further defy host cell offensives, M.tb opts for dormant phase, where it turns off or slows down most of its metabolic process as an added stratagem. While M.tb restrains most of its metabolic activities during dormancy, surprisingly latency-associated alpha-crystallin protein (Acr-1) is expressed most prominently during this phase. Interestingly, several previous studies described the potential of Acr-1 to induce the robust immuno-prophylactic response in the immunized host. It is intriguing to comprehend the apparent discrepancy that the microbe M.tb overexpresses a protein that has the potential to prime host immune system against the pathogen itself. Keeping this apparent ambiguity into consideration, it is imperative to unravel intricacies involved in the exploitation of Acr-1 by M.tb during its interaction with host immune cells. The present study suggests that Acr-1 exhibits diverse role in the maturation of macrophages (MΦs) and related immunological responses. The early encounter of bone marrow derived immune cells (pre-exposure during differentiation to MΦs) with Acr-1 (AcrMΦpre), results in hampering of their function. The pre-exposure of naïve MΦs with Acr-1 induces the expression of TIM-3 and IL-10. In contrast, exposure of fully differentiated MΦs to Acr-1 results in their down-modulation and induces the phosphorylation of STAT-1 and STAT-4 in host MΦs. Furthermore, Acr-1 mediated activation of MΦs results in the induction of Th1 and Th17 phenotype by activated T lymphocyte.

Tuberculosis: The success tale of less explored dormant Mycobacterium tuberculosis

“…In contrast to this, Mubin et al in 2018 reported that Acr-1 regulates and inhibits the maturation of differentiated macrophages while activating naïve macrophages via phosphorylation of STAT-1 and STAT-4. This is accompanied by the generation of M.tb-specific T cells that can prevent disease (Mubin et al, 2018). Being a dormancyassociated gene, Acr-1 primes the host immune system to mount an immune response against the bacteria.…”