Tolerogenic dendritic cells in chronic helminth infection

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• Dr Katie Smith, Institute of Infection and Immunology Research, University of Edinburgh
• Wednesday 06 May 2009, 12:30-13:30
• Lecture Theater, Department of Pathology, Tennis Court Road.

If you have a question about this talk, please contact Prof. Jim Kaufman.

Host: Nick Holmes (nh106@cam.ac.uk)

Parasites have evolved effective mechanisms to manipulate an immune response and prevent expulsion from the host. Most notably, some gut helminths can also downregulate T cell responses to inflammatory stimuli including asthmatic and allergic reactions through stimulation and expansion of Foxp3+ regulatory T cells. Experiments in our lab have shown that Foxp3+ regulatory T cell expansion in vitro can be linked to a TGF -beta-like activity present in the excretory/secretory products of the rodent gut helminth Heligmosomoides Polygyrus. Chronic persistence of the adult worm infection can be modified by use of a synthetic TGF -beta type 1 receptor inhibitor in vivo.

I am interested in the mechanisms underlying this Foxp3+ regulatory T cell expansion in vivo and have focused on whether antigen presenting cells such as dendritic cells are re-programmed to a tolerogenic, regulatory T cell inducing, phenotype following infection. I have found that chronic helminth infection is associated with the expansion of CD11c(lo) dendritic cells in the draining lymph nodes of the gut. These cells have a plasmacytoid dendritic cell phenotype, a distinct response to TLR ligation and present antigen to T cells far less efficiently on comparison to conventional CD11c(hi) dendritic cells. CD11c(lo) cells polarise naive T cells to distinct T cells lineages, encouraging the expansion of antigen-specific Foxp3 T cells and polarisation away from Th17 cells. These regulatory T cell changes could be inhibited with excess antigen or the retinoic acid receptor antagonist LE540 and are enhanced with recombinant TGF -beta. My research is now focusing on manipulating plasmacytoid dendritic cell populations in vivo and determining the cause for the changes in the CDllc(lo) and Foxp3+ T cell populations following infection. Ultimately, my interest is in understanding the immunological mechanisms underlying helminth persistence, to determine whether these conditions can be replicated to drive tolerance in vivo.

This talk is part of the Immunology in Pathology series.

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