AUTHOR=Bah Aïcha , Lacarrière Camille , Vergne Isabelle 

TITLE=Autophagy-Related Proteins Target Ubiquitin-Free Mycobacterial Compartment to Promote Killing in Macrophages

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=6

YEAR=2016

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2016.00053

DOI=10.3389/fcimb.2016.00053

ISSN=2235-2988

ABSTRACT=<p>Autophagy is a lysosomal degradative process that plays essential functions in innate immunity, particularly, in the clearance of intracellular bacteria such as <italic>Mycobacterium tuberculosis</italic>. The molecular mechanisms involved in autophagy activation and targeting of mycobacteria, in innate immune responses of macrophages, are only partially characterized. Autophagy targets pathogenic <italic>M. tuberculosis</italic> via a cytosolic DNA recognition- and an ubiquitin-dependent pathway. In this report, we show that non-pathogenic <italic>M. smegmatis</italic> 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 <italic>M. smegmatis</italic> does not rely on membrane damage, ubiquitination, or autophagy receptor recruitment. Lastly, <italic>M. smegmatis</italic> 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.</p>