Polymorphonuclear neutrophils (PMNs) are rapidly recruited to tissues upon injury or infection. There, they can encounter local and/or recruited immature dendritic cells (iDCs), a colocalization that could promote at least transient interactions and mutually influence the two leukocyte populations. Using human live blood PMNs and monocytederived iDCs, we examined if these leukocytes actually interacted and whether this influenced DC function. Indeed, coculture with live but not apoptotic PMNs led to up-regulation of membrane CD40, CD86, and human leukocyte antigen (HLA)-DR on DCs. Whereas CD40 up-regulation was dependent on soluble factors released by PMNs, as determined in cultures conducted in different chambers, cell contact was necessary for CD86 and HLA-DR up-regulation, a process that was inhibited by anti-CD18 antibodies, indicating that CD18 ligation was required. We also found that via a cell contact-dependent mechanism, DCs acquired Candida albicansderived antigens from live as well as from apoptotic PMNs and could thus elicit antigen-specific T lymphocyte responses. Altogether, our data demonstrate the occurrence of cross-talk between human PMNs and DCs and provide new insights into the immune processes occurring upstream of the interactions between DCs and T lymphocytes. J. Leukoc. Biol. 79: 977-988; 2006.