The game theory describes the interactions between two players and the pay-off from wining, losing or compromising. Mycobacterium tuberculosis (Mtb)-host interactions were used as an example for the application of the game theory to describe and predict the possibilities of victory for any players. The gene expression for eight main markers of host response and three Mtb virulence factors were assessed in broncho-alveolar lavage of TB + and TB patients. The game theory showed that a variety of paths exist that players can use, in response to the behaviour of the counterpart. Briefly, according to the "Nash equilibrium", Ag85B is the main virulence factor for Mtb in active phase, however it is the most immunogenic factor if the host can respond by high expression of T-bet and iNOS. In this situation, Mtb can express high levels of ESAT-6 and CFP10 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 134-times higher in TB + s than the TB s, and the T-bet expression, ~200-times higher in the TB s than the TB + s. Furthermore, Mtb-Ag85B had a strong positive association with CCR2, T-bet and iNOS, but had a negative correlation with IDO.
Introduction
19When two organisms, individuals, parties, teams, or even countries interact, the outcome 20 varies greatly, depending on the intention of each party involved 1 . Attempts to quantify these 21 interactions can be assessed, using game theory models. Game theory is a mathematical 22 framework, describing the outcome (pay-off) resulted from specific interactions (game) 23 between two individuals (players) 2,3 . In biologic context, game theory can describe 24 interactions between a host and its parasite through epigenetic strategies, and the resulting 25 pay-off from healthy, infected, or disease onset. The conflict is very complex, as both 26 organisms are responsible for resisting and helping the associated genus to survive. In other 27 words, host-microbe interactions are complex assemblies of large numbers of phenomena that 28 are interacting competitively under multifactorial environmental conditions 1-3 .
29Bacteria and its host under stress may carry out the sophisticated principles of game theory, in 30 order to decide whether to compromise or invade for elimination of the danger 4 . Rationality 31 of game theory indicates that each player in a particular game is motivated by maximizing his 32 own pay-off. Therefore, it is especially important for players to think about each other's 33 strategic choice and react accordingly 4 . Interactions between Mycobacterium tuberculosis 34 (Mtb) and human (players) are often included in the Mtb's strategies to invade host responses, 35 to replicate and persist within the host, and on the other hand, the host attempts to induce 36 appropriate responses to eliminate the infection 5 . Particularly, in case of Mtb infection these 37 interactions are in a strict completion, as the microbe has adapted to replic...
