Autophagy and Mycobacteria

Research themes

Mycobacteria are a large family of bacteria which are characterized by a unique cell envelope rich in exotic lipids and glycoconjugates with immunomodulatory and/or virulence properties. Even though most of mycobacteria are non-pathogenic, a couple of serious human pathogens belong to this family such as Mycobacterium tuberculosis and M.leprae, etiologic agents of Tuberculosis and Leprosy, respectively. Additionally, in the past two decades several nontuberculous mycobacteria, such as M.abscessus, have emerged as significant pathogens in patients with cystic fibrosis. Lastly, M.avium subspecies paratuberculosis is a persistent intracellular bacteria associated with Crohn’s disease. Pioneering research has shown that autophagy activation plays an important role in controlling mycobacteria intracellular growth in macrophages as well as in antigen presentation during M.bovis BCG vaccination in mice. However, the detailed molecular mechanisms involved in mycobacteria-induced autophagy and those developed by pathogenic mycobacteria to evade this process remain to be fully uncovered. Our group is interested in investigating the molecular and cellular interaction between this process and mycobacteria with a focus on M.tuberculosis using both in vitro and in vivo model systems. The three main goals of our research are:
– To identify and characterize bacterial and host factors involved in autophagy regulation
– To decipher the functions of autophagy and autophagy-related genes during infection
– To develop novel vaccines against M.tuberculosis based on autophagy
Complementary hypothesis- and data-driven approaches and different collaborations is/will be implemented to achieve these objectives. Overall, our work should bring new insights into the intricate interplay between host autophagy and pathogenic bacteria. This better understanding could help in designing innovative prophylactic and curative therapeutics based on autophagy manipulation for the fight against tuberculosis and other pathogens.

Publications

– Bah A. and Vergne I. Autophagy and Autophagy-Related Proteins in the Immunity against Mycobacterium tuberculosis. Forum on Immunopathological Diseases and Therapeutics (in press).
– Espert L., Beaumelle B., Vergne I. Autophagy in Mycobacterium tuberculosis and HIV infections. (2015) Front Cell Infect Microbiol. 5:49. eCollection 2015. (Review).
– Vergne I., Gilleron M., Nigou J. Manipulation of the endocytic pathway and phagocyte functions by Mycobacterium tuberculosis lipoarabinomannan. (2015) Front Cell Infect Microbiol. 4:187. eCollection 2014. (Review).
– Singh SB., Ornatowski W., Vergne I., Naylor J., Delgado M., Roberts E., Ponpuak M., Master S., Pilli M., White E., Komatsu M., Deretic V. (2010) Human IRGM regulates autophagy and cell-autonomous immunity functions through mitochondria. Nat Cell Biol. 12:1154-65.
– Ponpuak M., Davis AS., Roberts EA., Delgado MA., Dinkins C., Zhao Z., Virgin HW. 4th, Kyei GB., Johansen T., Vergne I., Deretic V. (2010) Delivery of cytosolic components by autophagic adaptor protein p62 endows autophagosomes with unique antimicrobial properties. Immunity. 32:329-41. Commented in Immunity: Selective macroautophagy for immunity. Christian Münz 2010 32:329
– Kyei GB., Dinkins C., Davis AS., Roberts E., Singh SB., Dong C., Wu L., Kominami E., Ueno T., Yamamoto A., Federico M., Panganiban A., Vergne I., Deretic V. Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yield in macrophages. J. Cell. Biol. 186:255-68. 2009. Cover art for journal issue. Commented in “In focus article”: HIV uses autophagy for its own means. Nicole LeBrasseur J. Cell Biol. 2009 186: 165.
– Vergne I., Roberts E., Elmaoued RA., Tosch V., Delgado MA., Proikas-Cezanne T., Laporte J., Deretic V. (2009) Control of autophagy initiation by phosphoinositide 3-phosphatase jumpy. Embo J. 28:2244-2258.
– Delgado M., Singh S., De Haro S., Master S., Ponpuak M., Dinkins C., Ornatowski W., Vergne I., Deretic V. (2009) Autophagy and pattern recognition receptors in innate immunity. Immunol Rev. 227:189-202. (Review).
– Vergne I., Singh S., Roberts E., Kyei G., Master S., Harris J., de Haro S., Naylor J., Davis A., Delgado M., V. Deretic. (2006) Autophagy in Immune Defense Against Mycobacterium tuberculosis. Autophagy. 2:175-8. (Review).

 

Composition de l'équipe

Isabelle Vergne (CR CNRS)
Aïcha Bah (Etudiante en thèse)