Cross presentation: exotic pathwaysCross presentation pathways in human dendritic cells

Abstract

In mice, many studies have shown that cDC1 are specialized for cross-presentation, due to specific functions of their endocytic pathway. Monocyte-derived DC (mo-DC) can also cross-present antigens directly in peripheral tissues. By contrast, in human, we and others have shown that cDC1, cDC2 and pDC all have the ability to cross-present. In particular, we have shown that all 3 subsets can transfer exogenous antigens into their cytosol. We have also addressed whether human in vivo-generated mo-DC can cross-present, using cells directly purified from peritoneal ascites. We show that both mo-DC and monocyte-derived macrophages (mo-Mac) cross-present efficiently, but are inefficient for transfering exogenous proteins into their cytosol. Inhibition of cysteine proteases, but not of proteasome, abolishes cross-presentation in mo-DC and mo-Mac. Collectively, our results indicate that human cDC and pDC use a cytosolic pathway for cross-presentation while monocyte-derived cells cross-present exclusively using a vacuolar pathway.