Dectin-1-triggered recruitment of light chain 3 protein to phagosomes facilitates major histocompatibility complex class II presentation of fungal-derived antigens.
Dectin-1 is a pattern recognition receptor that is important for innate immune responses against fungi in humans and mice. Dectin-1 binds to β-glucans in fungal cell walls and triggers phagocytosis, production of reactive oxygen by the NADPH oxidase, and inflammatory cytokine production which all contribute to host immune responses against fungi. Although the autophagy pathway was originally characterized for its role in the formation of double-membrane compartments engulfing cytosolic organelles and debris, recent studies have suggested that components of the autophagy pathway may also participate in traditional phagocytosis. In this study, we show that Dectin-1 signaling in macrophages and bone marrow-derived dendritic cells triggers formation of LC3II, a major component of the autophagy machinery. Further, Dectin-1 directs the recruitment of LC3II to phagosomes, and this requires Syk, activation of reactive oxygen production by the NADPH oxidase, and ATG5. Using LC3-deficient dendritic cells we show that whereas LC3 recruitment to phagosomes is not important for triggering phagocytosis, killing or Dectin-1-mediated inflammatory cytokine production, it facilitates recruitment of MHC class II molecules to phagosomes and promotes presentation of fungal-derived antigens to CD4 T cells.
Division of Immunology, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Jun
J
Ma
Courtney
C
Becker
Clifford A
CA
Lowell
David M
DM
Underhill
D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D000946:Antigens, Fungal / Q000276:immunology* / Q000378:metabolism; D000071187:Autophagy-Related Protein 5; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019255:NADPH Oxidases / Q000235:genetics / Q000276:immunology; D010588:Phagosomes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000072377:Syk Kinase; D047071:beta-Glucans / Q000276:immunology* / Q000378:metabolism; D000099181:Dectin-1
D000946:Antigens, Fungal; D000071187:Autophagy-Related Protein 5; D000949:Histocompatibility Antigens Class II; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008869:Microtubule-Associated Proteins; D019255:NADPH Oxidases; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; D047071:beta-Glucans; D000099181:Dectin-1; C495773:Atg5 protein, mouse; C480860:Map1lc3b protein, mouse; C000606896:SYK protein, human; C000606897:Syk protein, mouse