Author:
Lin Ching-Yu,Nozawa Takashi,Minowa-Nozawa Atsuko,Toh Hirotaka,Hikichi Miyako,Iibushi Junpei,Nakagawa Ichiro
Abstract
Bacterial autophagy—a type of macroautophagy that is also termed xenophagy—selectively targets intracellular bacteria such as group A Streptococcus (GAS), a ubiquitous pathogen that causes numerous serious diseases, including pharyngitis, skin infections, and invasive life-threatening infections. Although bacterial autophagy is known to eliminate invading bacteria via the action of autophagy receptors, the underlying mechanism remains unclear. Herein, we elucidated that Tollip functions as a bacterial-autophagy receptor in addition to participating involved in the intracellular immunity mechanism that defends against bacterial infection. Tollip was recruited to GAS-containing endosomal vacuoles prior to the escape of GAS into the cytosol; additionally, Tollip knockout disrupted the recruitment of other autophagy receptors, such as NBR1, TAX1BP1, and NDP52, to GAS-containing autophagosomes and led to prolonged intracellular survival of GAS. Furthermore, Tollip was found to be required for the recruitment of galectin-1 and -7 to GAS-containing autophagosomes, and immunoprecipitation results indicated that Tollip interacts with galectin-7. Lastly, our data also revealed that galectin-1 and -7 are involved in the restriction of GAS replication in cells. These results demonstrated that Tollip modulates bacterial autophagy by recruiting other autophagy receptors and galectins.
Funder
Ministry of Education, Culture, Sports, Science and Technology
Takeda Science Foundation
Japan Agency for Medical Research and Development
Subject
Infectious Diseases,Microbiology (medical),Immunology,Microbiology
Cited by
18 articles.
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