Game theory applications in host-microbe interactions toward disease manifestation: Mycobacterium tuberculosis infection as an example | ||
| Iranian Journal of Basic Medical Sciences | ||
| دوره 24، شماره 10، دی 2021، صفحه 1324-1335 اصل مقاله (973.32 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2021.55471.12410 | ||
| نویسندگان | ||
| Hiva Sharebiani1؛ Sara Hajimiri1؛ Shadi Abbasnia1، 2؛ Saman Soleimanpour2، 3؛ Amir Mohamad Hashem Asnaashari4؛ Narges Valizadeh1؛ Mohammad Derakhshan2، 3؛ Rezvan Pilpa2، 3؛ Arezoo Firouzeh2، 3؛ Kiarash Ghazvini2، 3؛ Saeid Amel JamehDar2، 3؛ Seyed Abdolrahim Rezaee* 1 | ||
| 1Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran | ||
| 2Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran | ||
| 3Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran | ||
| 4Lung Disease Research Center, Mashhad University of Medical Science, Mashhad, Iran | ||
| چکیده | ||
| 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 (CCR1, CCR2, IDO, Tbet, TGFβ, iNOS, MMP3, MMP9) of host response and three Mtb virulence factors (Ag85B, CFP-10, ESAT-6) were assessed in broncho-alveolar lavage of TB+ and TB- patients. Results: The players’ strategies in the “Nash equilibrium”, showed that Ag85B 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 Th1 response. 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. Conclusion: Ag85B and maybe ESAT6 (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 Th1 responses. | ||
| کلیدواژهها | ||
| Game theory؛ M. tuberculosis antigens؛ Mycobacterium tuberculosis؛ Th1؛ Tuberculosis | ||
| مراجع | ||
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