Dendritic cells (DCs) play a decisive role in immunity; they
interact with various pathogens via several pattern recognition
and different opsonophagocytotic receptors, including Fc- and
complement-receptors. beta2-integrins, including complement
receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18) participate in
many immunological processes, especially those involving cell
migration, adherence, and phagocytosis. Human monocyte derived
dendritic cells (MDCs) are known to express CR3 as well as CR4,
however possible differences regarding the role of these
receptors has not been addressed so far. Our aim was to explore
whether there is a difference between the binding and uptake of
various complement-opsonized microorganisms, mediated by CR3 and
CR4. Studying the expression of receptors during differentiation
of MDCs we found that the appearance of CD11b decreased, whereas
that of CD11c increased. Interestingly, both receptors were
present in the cell membrane in an active conformation. Here we
demonstrate that ligation of CD11b directs MDCs to enhanced
phagocytosis, while the maturation of the cells and their
inflammatory cytokine production are not affected. Blocking
CD11c alone did not change the uptake of opsonized yeast or
bacteria by MDCs. We confirmed these results using siRNA; namely
downregulation of CD11b blocked the phagocytosis of microbes
while silencing CD11c had no effect on their uptake. Our data
clearly demonstrate that complement C3-dependent phagocytosis
of MDCs is mediated mainly by CR3
