Regulation of dendritic cell function by pathogen-derived molecules plays a key role in dictating the outcome of the adaptive immune response

Abstract

There is increasing awareness that dendritic cells (DCs) can interpret pathogen-inherent signals and play a pivotal role in polarizing Th cell differentiation. Polarized Th1 responses are induced by DCs, which respond to pathogen-derived TLR ligands to mature and produce IL-12 and related cytokines that are instrumental in Th1 cell outgrowth. In contrast, DCs exposed to SEA (soluble egg Ag from the helminth parasite Schistosoma mansoni) retain a (modified) immature phenotype and induce Th2 responses. In addition to providing positive signals for Th1 cell development, DCs activated to mature by TLR-engagement also provide a potent negative signal that prevents the development of Th2 cells. Production of this signal is dependent upon a MyD88-dependent signaling pathway in DCs. In contrast, exposure of DCs to SEA severely limits their ability to respond to inflammatory TLR ligands such as LPS and CpG. Thus as part of their pathogen-specific response programs, DC can exert negative as well as positive signals for Th response polarization. These effects may have powerful and systemic effects on disease outcome.