Filarial antigens impair the function of human dendritic cells during differentiation

The antigen-specific T-cell unresponsiveness seen in lymphatic filariasis i s mediated, in part, by diminished antigen-presenting cell function and is most specific for microfilariae (MF), the parasite stage found in large num bers in the peripheral circulation. We investigated the effect of MF antige n (MFAg) on dendritic cells (DC) in both their differentiation process from monocyte precursors and also after they have developed into DC. When MFAg was added to cultures of monocytes during their; differentiation process to immature DC, the production of interleukin 12 (IL-12) p40, p70 protein, an d IL-10 was significantly (P < 0.03) inhibited in response to Staphylococcu s aureus Cowan (SAC) and SAC-gamma interferon (IFN-<gamma>) (60% to 80% inh ibition). IL-10 was also inhibited (P = 0.04) in response to CD40 ligand-IF N-gamma. Moreover, MFAg inhibited the mRNA expression of IL-12 p40 and IL-1 0 as assessed by RNA protection assays. This effect was antigen specific, a s another parasite antigen (soluble Toxoplasma gondii antigen) did not inhi bit the production of these cytokines. This effect was also not a result of diminished cell viability nor of an alteration in surface expression of mo st costimulatory surface molecules, including major histocompatibility comp lex class I and class II. In contrast to exposure throughout the differenti ation process, MFAg added to immature DC had no effect on DC cytokine expre ssion. Although NIF-differentiated DC were capable of inducing an allogenei c mixed lymphocyte reaction, they did so to a significantly lesser degree t han DC without antigen exposure. These data collectively suggest that once DC are differentiated from their precursor cells, they become resistant to changes by MFAg.