Autophagy in innate and adaptive immunity against intracellular pathogens.
Autophagy delivers cytoplasmic constituents for lysosomal degradation. Recent studies have demonstrated that this pathway mediates resistance to pathogens and is targeted for immune evasion by viruses and bacteria. Lysosomal degradation products, including pathogenic determinants, are then surveyed by the adaptive immune system to elicit antigen-specific T cell responses. CD4(+) T helper cells have been shown to recognize nuclear and cytosolic antigens via presentation by major histocompatibility complex (MHC) class II molecules after autophagy. Furthermore, some sources of natural MHC class II ligands display characteristics of autophagy substrates, and autophagosomes fuse with late endosomes, in which MHC class II loading is thought to occur. Although MHC class II antigen processing via autophagy has so far mainly been described for professional antigen-presenting cells like B cells, macrophages, and dendritic cells, it might be even more important for cells with less endocytic potential, like epithelial cells, when these express MHC class II at sites of inflammation. Therefore, autophagy might contribute to immune surveillance of intracellular pathogens via MHC class II presentation of intracellular pathogen-derived peptides.
Schmid
Dorothee
D
Laboratory of Viral Immunobiology, and Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10021, USA.
Dengjel
Jörn
J
Schoor
Oliver
O
Stevanovic
Stefan
S
Münz
Christian
C
D000222:Adaptation, Physiological / Q000276:immunology*; D000818:Animals; D001343:Autophagy; D001424:Bacterial Infections / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003593:Cytoplasm / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007239:Infections / Q000276:immunology* / Q000473:pathology*; D008247:Lysosomes / Q000378:metabolism
D000949:Histocompatibility Antigens Class II