Professor in Immunology
Institut Pasteur de Tunis
Research area keywords
TB, vaccines, animal models, clinical trials, HDT
Makram Essafi is leading a group working on the role of host innate response in the establishment of an efficient adaptive immune one against TB. The major aim is to uncover the host factors involved in such response to help generating tools to be used either as adjuncts for the standard treatment of TB or as adjuvants to enhance the efficacy of BCG. The data we generated led us to work on the development of better versions of BCG vaccine to prevent/treat Tuberculosis. Our approach consists of optimizing the host innate immune response (apoptosis, phagosome/cytosol translocation and IL-10 secretion) towards the establishment of an efficient CD8-mediated adaptive immune response. We found that a such response is enhanced through the activation of the host FOXO3 transcription factor, leading to both, the increase of BCG-induced apoptosis of infected macrophages and the inhibition of the immunomodulatory cytokine IL-10. At this stage we would like to get engaged in a large network of investigators interested in the pre- and clinical validation of the vaccination procedure we developed. Moreover, we are interested in developing host-directed approaches to treat TB based on FOXO3 activation.
- Rania Bouzeyen, Saurabh Chugh, Tannu Priya Gosain , Mohamed-Ridha Barbouche, Meriam Haoues, Kanury V.S. Rao, Makram Essafi † and Ramandeep Singh † . Co-administration of Akt inhibitor MK-2206 enhances the efficacy of BCG vaccine against Mycobacterium tuberculosis in mice and guinea pigs. In press Front Immunol 2021 doi: 10.3389/fimmu.2021.645962. † Co-senior and corresponding authors
- Rania Bouzeyen, M Haoues, MR Barbouche, R Singh and M Essafi. FOXO3 Transcription Factor Regulates IL-10 Expression in Mycobacteria-Infected Macrophages, Tuning Their Polarization and the Subsequent Adaptive Immune Response. Front Immunol. 2019 Dec 12;10:2922. doi: 10.3389/fimmu.2019.02922.
- Amira Refai, Sami Gritli, Mohamed-Ridha Barbouche and Makram Essafi. Mycobacterium tuberculosis Virulent Factor ESAT-6 Drives Macrophage Differentiation Toward the Pro-inflammatory M1 Phenotype and Subsequently Switches It to the Anti-inflammatory M2 Phenotype Frontiers in Cellular and Infection Microbiology. DOI: 10.3389/fcimb.2018.00327
- Haoues M, Refai A, Mallavialle A, Barbouche MR, Laabidi N, Deckert M and Essafi M. Forkhead box O3 (FOXO3) Transcription Factor mediates Apoptosis in BCG-Infected Macrophages. Cell Microbiol. 2014 Apr 8. doi: 10.1111/cmi.12298
- Hanene Sahli, Aymen Mouelhi, Mohamed Fethi Diouani, Lotfi Tlig, Amira Refai,Ramzi Boubaker Landoulsi, Mounir Sayadi and Makram Essafi . An advanced intelligent ELISA test for bovine tuberculosis diagnosis. Biomedical Signal Processing and Control 46 (2018) 59–66. Diouani MF, Ouerghi O, Refai A, Belgacem K, Tlili C, Laouini D, Essafi M. Detection of ESAT-6 by a label free miniature immuno-electrochemical biosensor as a diagnostic tool for tuberculosis. Mater Sci Eng C Mater Biol Appl. 2017 May 1;74:465-470.
- Refai A, Haoues M, Othman H, Barbouche MR, Moua P, Bondon A, Mouret L, Srairi-Abid N, Essafi M. Two distinct conformational states of Mycobacterium tuberculosis virulent factor ESAT-6 are behind the discrepancy around its biological functions. FEBS J. 2015 Nov;282(21):4114-29.
- Patent N°: TN2013/0198: Use of FOXO3 activators to prevent/treat Tuberculosis in mammals. Inventors: Makram Essafi and Meriam Haoues