title: Parasite Proximity Drives the Expansion of Regulatory T Cells in Peyer's Patches following Intestinal Helminth Infection.
abstract: Helminth infections are typically chronic in nature; however, the exact molecular mechanisms by which these parasites promote or thwart host immunity remain unclear. Worm expulsion requires the differentiation of CD4(+) T cells into Th2 cells, while regulatory T cells (Tregs) act to dampen the extent of the Th2 response. Priming of T cells requires drainage or capture of antigens within lymphoid tissues, and in the case of intestinal helminths, such sites include the mucosa-associated Peyer's patches (PPs) and the draining mesenteric lymph nodes (MLN). To gain insight into when and where the activation of the adaptive T cell response takes place following intestinal helminth infection, we analyzed Th2 and Treg responses in the PPs and MLN following infection with the murine intestinal helminth Heligmosomoides polygyrus bakeri. Protective Th2 responses were observed to be largely restricted to the MLN, while a greater expansion of Tregs occurred within the PPs. Interestingly, those PPs that formed a contact with the parasite showed the greatest degree of Treg expansion and no evidence of type 2 cytokine production, indicating that the parasite may secrete products that act in a local manner to selectively promote Treg expansion. This view was supported by the finding that H. polygyrus bakeri larvae could promote Treg proliferation in vitro. Taken together, these data indicate that different degrees of Treg expansion and type 2 cytokine production occur within the PPs and MLN following infection with the intestinal helminth H. polygyrus bakeri and indicate that these organs exhibit differential responses following infection with intestinal helminths.
authors.affiliation: Global Health Institute, Department of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Mosconi
authors.affiliation: Global Health Institute, Department of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Lalit Kumar
authors.initials: LK
authors.lastname: Dubey
authors.affiliation: Global Health Institute, Department of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Volpe
authors.affiliation: Global Health Institute, Department of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Julia
authors.initials: J
authors.lastname: Esser-von Bieren
authors.affiliation: Global Health Institute, Department of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Mario M
authors.initials: MM
authors.lastname: Zaiss
authors.affiliation: Global Health Institute, Department of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Luc
authors.initials: L
authors.lastname: Lebon
authors.affiliation: Global Health Institute, Department of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Joanna C
authors.initials: JC
authors.lastname: Massacand
authors.affiliation: Global Health Institute, Department of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland nicola.harris@epfl.ch.
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Harris
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006373:Helminthiasis / Q000276:immunology*; D007411:Intestinal Diseases, Parasitic / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009351:Nematospiroides dubius / Q000276:immunology; D010581:Peyer's Patches / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D017206:Strongylida Infections / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology