Game theory applications in host-microbe interactions toward disease manifestation: Mycobacterium tuberculosis infection as an example

Objective(s): Game theory describes the interactions between two players and the pay-off from winning, losing, or compromising. In the present study, Mycobacterium tuberculosis (Mtb)–host interactions were used as an example for the application of game theory to describe and predict the different outcomes of Mtb-infection and introducing target molecules for use in protection or therapy.Materials and Methods: The gene expression for eight main markers (CCR۱, CCR۲, IDO, Tbet, TGFβ, iNOS, MMP۳, MMP۹) of host response and three Mtb virulence factors (Ag۸۵B, CFP-۱۰, ESAT-۶) were assessed in broncho-alveolar lavage of TB+ and TB- patients.Results: The players’ strategies in the “Nash equilibrium”, showed that Ag۸۵B is the main virulence factor for Mtb in active phase, and also the most immunogenic factor, if the host can respond by high expression of T-bet and iNOS toward a Th۱ response. In this situation, Mtb can express high levels of ESAT-۶ and CFP۱۰ and change the game to the latency, in which host responses by medium expression of T-bet and iNOS and medium level of TGF-β and IDO. Consistently, the IDO expression was ۱۳۴-times higher in TB+s than the TB-s,and the T-bet expression,~۲۰۰-times higher in the TB-s than the TB+s. Furthermore, Mtb-Ag۸۵B had a strong positive association with CCR۲, T-bet and iNOS, but had a negative correlation with IDO.Conclusion: Ag۸۵B and maybe ESAT۶ (without its suppressive C-terminal) should be considered for making subunit vaccines. And, preventing IDO formation in dendritic cells might be a novel target for immunotherapy of tuberculosis, to reduce the pressure of immune-suppression on Th۱ responses.

Keywords:

Game theory , M. tuberculosis antigens , Mycobacterium tuberculosis , Th۱ , Tuberculosis