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

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 CD11clowCD45RBmid subset increased rapidly following H. polygyrus infection and the CD11cmidCD45RBhigh 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, CD11clowCD45RBmid DCs induced a low proliferation response and a high level of IL-10 production in CD4+ T cells, whereas CD11cmidCD45RBhigh DCs induced more IFN-γ and IL-4 producing CD4+ T cells. Intracellular staining revealed that CD11clowCD45RBmid DCs promoted CD4+ Foxp3+ differentiations. These results indicate that nematode infections selectively induce expansion of the CD11clowCD45RBmid 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.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (96 K)Download as PowerPoint slideHighlights► Nematode parasite infections induce immunosuppression. ► A regulatory dendritic cell subset was identified in MLN of mice infected with nematode parasite Heligmosomoides polygyrus. ► This regulatory DC subset shows CD11clowCD45RBmid phenotype and promotes Foxp3+ Treg differentiation and IL-10 production. ► These findings provide a link between nematode infection, Treg cell response and subsequent immunosuppression.