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innate and adaptive immunity • influenza virus • mycobacterium tuberculosis • Coronavirus
Our lab focuses on investigating the cellular and molecular mechanisms involved in the cross-talk between innate and adaptive immunity to major pulmonary infectious diseases, such as influenza and tuberculosis. Host survival during infection in vital organs, such as the lung, requires a delicate balance between host resistance, which is essential for detecting and eliminating the pathogens, and disease tolerance, which is critical in minimizing collateral tissue damage. We are also investigating how to harness the power of innate immunity in vaccine via reprogramming of hematopoietic stem cells. In summary, understanding the regulatory mechanisms involved in both host-resistance and tolerance is essential for the future development of an effective therapy or vaccine.
Kaufmann E, Sanz J, Dunn JL, Khan N, Mendonça LE, Pacis A, Tzelepis F, Pernet E, Dumaine A, Grenier JC, Mailhot-Léonard F, Ahmed E, Belle J, Besla R, Mazer B, King IL, Nijnik A, Robbins CS, Barreiro LB, Divangahi M. BCG Educates Hematopoietic Stem Cells to Generate Protective Innate Immunity against Tuberculosis. Cell. 2018 Jan 11;172(1-2):176-190.e19. doi: 10.1016/j.cell.2017.12.031. PMID: 29328912.
Khan N, Mendonca L, Dhariwal A, Fontes G, Menzies D, Xia J, Divangahi M, King IL. Intestinal dysbiosis compromises alveolar macrophage immunity to Mycobacterium tuberculosis. Mucosal Immunol. 2019 May;12(3):772-783. doi: 10.1038/s41385-019-0147-3. Epub 2019 Feb 19. PMID: 30783183.
Pernet E, Downey J, Vinh DC, Powell WS, Divangahi M. Leukotriene B 4-type I Interferon Axis Regulates Macrophage-Mediated Disease Tolerance to Influenza Infection. Nat Microbiol. 2019 Aug;4(8):1389-1400. doi: 10.1038/s41564-019-0444-3. Epub 2019 May 20. PMID: 31110361.
Downey J, Pernet E, Coulombe F, Divangahi M. Dissecting host cell death programs in the pathogenesis of influenza. Microbes Infect. 2018 Oct-Nov;20(9-10):560-569. doi: 10.1016/j.micinf.2018.03.005. Epub 2018 Apr 18. PMID: 29679740.
Netea MG, Domínguez-Andrés J, Barreiro LB, Chavakis T, Divangahi M, Fuchs E, Joosten LAB, van der Meer JWM, Mhlanga MM, Mulder WJM, Riksen NP, Schlitzer A, Schultze JL, Stabell Benn C, Sun JC, Xavier RJ, Latz E. Defining trained immunity and its role in health and disease. Nat Rev Immunol. 2020 Mar 4. doi: 10.1038/s41577-020-0285-6. Online ahead of print. PMID: 32132681.