title: Autophagy-Related Proteins Target Ubiquitin-Free Mycobacterial Compartment to Promote Killing in Macrophages.
abstract: Autophagy is a lysosomal degradative process that plays essential functions in innate immunity, particularly, in the clearance of intracellular bacteria such as Mycobacterium tuberculosis. The molecular mechanisms involved in autophagy activation and targeting of mycobacteria, in innate immune responses of macrophages, are only partially characterized. Autophagy targets pathogenic M. tuberculosis via a cytosolic DNA recognition- and an ubiquitin-dependent pathway. In this report, we show that non-pathogenic M. smegmatis induces a robust autophagic response in THP-1 macrophages with an up regulation of several autophagy-related genes. Autophagy activation relies in part on recognition of mycobacteria by Toll-like receptor 2 (TLR2). Notably, LC3 targeting of M. smegmatis does not rely on membrane damage, ubiquitination, or autophagy receptor recruitment. Lastly, M. smegmatis promotes recruitment of several autophagy proteins, which are required for mycobacterial killing. In conclusion, our study uncovered an alternative autophagic pathway triggered by mycobacteria which involves cell surface recognition but not bacterial ubiquitination.
authors.affiliation: Tuberculosis and Infection Biology, Institut de Pharmacologie et de Biologie Structurale, UMR 5089 Centre National de la Recherche Scientifique - Université de Toulouse Toulouse, France.
authors.forename: Aïcha
authors.initials: A
authors.lastname: Bah
authors.affiliation: Tuberculosis and Infection Biology, Institut de Pharmacologie et de Biologie Structurale, UMR 5089 Centre National de la Recherche Scientifique - Université de Toulouse Toulouse, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Lacarrière
authors.affiliation: Tuberculosis and Infection Biology, Institut de Pharmacologie et de Biologie Structurale, UMR 5089 Centre National de la Recherche Scientifique - Université de Toulouse Toulouse, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vergne
mesh_terms: D000071183:Autophagy-Related Proteins / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D020102:Mycobacterium smegmatis / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D000071183:Autophagy-Related Proteins; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D025801:Ubiquitin
keywords: autophagy; innate immunity; macrophage; mycobacterium; phagosome; toll-like receptor; ubiquitin