In Vivo Requirement for Atg5 in Antigen Presentation by Dendritic Cells

• Published in: Immunity (Cambridge, Mass.) Vol. 32; no. 2; pp. 227 - 239
• Main Authors: Lee, Heung Kyu, Mattei, Lisa M., Steinberg, Benjamin E., Alberts, Philipp, Lee, Yun Hee, Chervonsky, Alexander, Mizushima, Noboru, Grinstein, Sergio, Iwasaki, Akiko
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26-02-2010; Elsevier Limited
• Subjects: Animals; Antigen Presentation - genetics; Autophagy; Autophagy-Related Protein 5; CELLIMMUNO; Cells, Cultured; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - pathology; Female; Herpes Simplex - immunology; Herpes simplex virus; Herpesvirus 2, Human - immunology; Histocompatibility Antigens Class II - metabolism; Immune system; Kinases; Lymphocyte Activation - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - immunology; Microtubule-Associated Proteins - metabolism; MOLIMMUNO; Peptides; Proteins; Radiation Chimera; RNA, Small Interfering - genetics; Scholarships & fellowships; Brazil; MOLIMMUNO; CELLIMMUNO
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2009.12.006

Autophagy is known to be important in presentation of cytosolic antigens on MHC class II (MHC II). However, the role of autophagic process in antigen presentation in vivo is unclear. Mice with dendritic cell (DC)-conditional deletion in Atg5, a key autophagy gene, showed impaired CD4
+ T cell priming after herpes simplex virus infection and succumbed to rapid disease. The most pronounced defect of
Atg5
−/− DCs was the processing and presentation of phagocytosed antigens containing Toll-like receptor stimuli for MHC class II. In contrast, cross-presentation of peptides on MHC I was intact in the absence of Atg5. Although induction of metabolic autophagy did not enhance MHC II presentation, autophagic machinery was required for optimal phagosome-to-lysosome fusion and subsequent processing of antigen for MHC II loading. Thus, our study revealed that DCs utilize autophagic machinery to optimally process and present extracellular microbial antigens for MHC II presentation.
► DCs use autophagy machinery to process exogenous microbial antigens for MHC II ► Canonical autophagy is not required for processing of phagocytosed antigens ► Mice with Atg5 deletion in DCs fail to induce Th1 cells and succumb to HSV infection