Game Theory Applications in Host-Microbe Interactions:Mycobacterium tuberculosisinfection as an example

Abstract

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...

Production and Evaluation of Ag85B:HspX:hFcγ1 Immunogenicity as an Fc Fusion Recombinant Multi-Stage Vaccine Candidate Against Mycobacterium tuberculosis

“…In our previous M.tb-host study in TB-positive and TB-negative patients, the gene expression assessments showed that the main virulence factor of M.tb was Ag85B and the complex of ESAT-6-CFP-10 that M.tb uses to combat host responses. On the other hand, the effective host's response to eliminate M.tb was a Th1 cellular immune response, mainly against the predominant M.tb antigen (Ag85), implicating in the polarization of the response by the expression of transcription factor (T-bet), modulatory factors (IDO and FoxP3) and activation of effector macrophages, activating oxygen-dependent pathway, iNOS and proteolytic activities (Sharebiani et al 2020). Therefore, Ag85 was used as the most virulence factor for activation and dissemination of M.tb, while it is the most immunodominant Ag for host immune responses to produce protective immunity.…”

Mycobacterium tuberculosis and host interactions in the manifestation of tuberculosis

“…They are the main cytokines in host defense against M.tb to potentiate the functions of macrophages, NK cells, and CTLs. This host response powerfully eliminates the M.tb and may establish a specific protective immunity [15] , [16] .…”

“…Most of these molecules are strong immunogenes that the host can respond to and eliminate the infection. Many other mechanisms have also been involved in the ability of M.tb to arrest phagosome maturation, DC1 forming, and Th1 differentiating [16] , but our understanding of these mechanisms remains incomplete. The host’s main immunological molecules can be considered in four different stages as the host’s strategies: (i) inflammatory reactions and leukocyte recruitment by CCRs (CCR1-7, and CXCR1,2) in response to secretion of inflammatory cytokines such as IL-1β, TNF-α, Il-6, IFN-I, IL-10, CCL-1–5, CXCL-1,-2,-3,-5,-6,-7,-8, On the other hand, the host's critical immune molecules which can play pivotal roles in the host responses toward TB manifestation, fulminant disease, latency or exacerbation including [53] .…”

“…(iv) elimination of infection or TB development by release of effector molecules in tissue damage. These conditions can be changed depending on host (human) or microbe ( M.tb ) activities under the influence of epigenetic strategies [16] , [55] .…”

Modelling of Interaction Dynamics of a Pathogen and Bio-Markers (Matrix Metalloproteinases) of Tissue Destruction in Pulmonary Tuberculosis

“…The model, comprised of three ordinary differential equations built by the authors of the work [24], is devoted to the the activation of the inflammatory process, where MMPs are considered within a generalized variable, which takes into account complex pro-inflammatory mediators. The game-theoretical approach to the dynamics of a medium-size network of the hostpathogen interactions determined from the gene expressions (including those, which code MMPs) in samples taken from a cohort of patients was considered in the work [25]. Additionally, a differential-equation-based model for the macrophage proinflammatory response against M. tuberculosis, including granuloma's dynamics, among the factors of which MMP-9 was considered, was constructed and analysed in work [26].…”