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2018 ; 9
(1
): 2570
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Human in vivo-generated monocyte-derived dendritic cells and macrophages
cross-present antigens through a vacuolar pathway
#MMPMID29967419
Tang-Huau TL
; Gueguen P
; Goudot C
; Durand M
; Bohec M
; Baulande S
; Pasquier B
; Amigorena S
; Segura E
Nat Commun
2018[Jul]; 9
(1
): 2570
PMID29967419
show ga
Presentation of exogenous antigens on MHC-I molecules, termed cross-presentation,
is essential for cytotoxic CD8(+) T cell responses. In mice, dendritic cells
(DCs) that arise from monocytes (mo-DCs) during inflammation have a key function
in these responses by cross-presenting antigens locally in peripheral tissues.
Whether human naturally-occurring mo-DCs can cross-present is unknown. Here, we
use human mo-DCs and macrophages directly purified from ascites to address this
question. Single-cell RNA-seq data show that ascites CD1c(+) DCs contain
exclusively monocyte-derived cells. Both ascites mo-DCs and monocyte-derived
macrophages cross-present efficiently, but are inefficient for transferring
exogenous proteins into their cytosol. Inhibition of cysteine proteases, but not
of proteasome, abolishes cross-presentation in these cells. We conclude that
human monocyte-derived cells cross-present exclusively using a vacuolar pathway.
Finally, only ascites mo-DCs provide co-stimulatory signals to induce effector
cytotoxic CD8(+) T cells. Our findings thus provide important insights on how to
harness cross-presentation for therapeutic purposes.