The phenotype and function of naturally existing regulatory dendritic cells in nematode-infected mice

Abstract

Immunosuppression associated with chronic helminth infections has been documented in many studies and regulatory T (Treg) cells have been shown to mediate the nematode-induced immunosuppression, but the role of dendritic cells (DCs) in the induction of Treg cell response and immunosuppression has not yet been fully determined. We analysed the response and function of DCs in mesenteric lymph node (MLNs) of mice infected with a gastrointestinal nematode, Heligmosomoides polygyrus, and observed a substantial expansion of DCs in MLNs following the infection. The CD11c + DCs in MLNs of infected mice showed reduced expression of co-stimulatory molecules CD40, CD86 and MHC-II, and production of inflammatory cytokines IL-12 and IL-6. Analysis of MLN DC subsets defined by CD11c and CD45RB expression showed that the CD11c lowCD45RB mid subset increased rapidly following H. polygyrus infection and the CD11c midCD45RB high subset expanded from the third week after infection. In the co-culture of sorted DC subsets with ovalbumin-(OVA-)specific T cell receptor (TCR) transgenic CD4 + T cells, CD11c lowCD45RB mid DCs induced a low proliferation response and a high level of IL-10 production in CD4 + T cells, whereas CD11c midCD45RB high DCs induced more IFN-γ and IL-4 producing CD4 + T cells. Intracellular staining revealed that CD11c lowCD45RB mid DCs promoted CD4 + Foxp3 + differentiations. These results indicate that nematode infections selectively induce expansion of the CD11c lowCD45RB mid regulatory DC subset that promotes development of Foxp3 + and IL-10 producing Treg cells. The Treg cell responses and immunoregulatory cytokines induced by this regulatory DC subset in turn play an important role in mediation of the nematode-induced immunosuppression.