Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-04686-8
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- Ligue Nationale Contre le Cancer (Equipe Labellisee)
- ERC
- ANR
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Cross-presentation allows exogenous antigen presentation in association with major histocompatibility complex class I molecules, a process crucial for the priming of CD8(+) T-cell responses against viruses and tumors. By contrast to conventional dendritic cells (cDC), which cross-present antigens in the steady state, plasmacytoid dendritic cells (pDC) acquire this ability only after stimulation by Toll-like receptor (TLR) ligands. The intracellular pathways accounting for this functional difference are still unknown. Here we show that the induction of cross-presentation by pDCs is regulated by mitochondria through a reactive oxygen species (ROS)-dependent mechanism, involving pH alkalization and antigen protection. The reduction of mitochondrial ROS production dramatically decreases the cross-presentation capacity of pDCs, leading to a strong reduction of their capacity to trigger CD8(+) T-cell responses. Our results demonstrate the importance of mitochondrial metabolism in pDC biology, particularly for the induction of adaptive immune responses.
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