Autophagy regulates long-term cross-presentation by murine dendritic cells

Area of Science:

• Immunology
• Cell Biology

Background:

• Dendritic cells (DCs) are crucial for antigen cross-presentation to CD8+ T cells.
• Autophagy is implicated in supporting antigen cross-presentation by DCs.
• DCs can store antigens long-term in endolysosomal compartments for sustained cross-presentation.

Purpose of the Study:

• To investigate the specific role of autophagy in the long-term antigen presentation capacity of DCs.
• To determine how autophagy machinery affects antigen storage and subsequent cross-presentation.

Main Methods:

• Utilized autophagy-deficient (Atg5-/-) dendritic cells (DCs).
• Treated DCs with common autophagy inhibitors.
• Assessed antigen storage duration and MHCI antigen cross-presentation efficiency.
• Examined the proximity of antigen storage compartments to LC3-positive autophagosomes.

Main Results:

• Autophagy deficiency or inhibition enhanced antigen storage within DCs.
• Autophagy-deficient DCs exhibited augmented long-term antigen cross-presentation to CD8+ T cells.
• This enhancement was independent of proteasome activity or MHCI surface expression.
• Autophagosomes were observed in close proximity to antigen storage compartments.

Conclusions:

• Autophagy machinery negatively regulates antigen storage in DCs.
• Autophagosomes disrupt antigen storage, thereby controlling long-term MHCI cross-presentation.
• Modulating autophagy could be a strategy to enhance DC-mediated antigen presentation.