title: Cutting Edge: the BTLA-HVEM regulatory pathway interferes with protective immunity to intestinal Helminth infection.
abstract: Helminths exploit intrinsic regulatory pathways of the mammalian immune system to dampen the immune response directed against them. In this article, we show that infection with the parasitic nematode Strongyloides ratti induced upregulation of the coinhibitory receptor B and T lymphocyte attenuator (BTLA) predominantly on CD4(+) T cells but also on a small fraction of innate leukocytes. Deficiency of either BTLA or its ligand herpes virus entry mediator (HVEM) resulted in reduced numbers of parasitic adults in the small intestine and reduced larval output throughout infection. Reduced parasite burden in BTLA- and HVEM-deficient mice was accompanied by accelerated degranulation of mucosal mast cells and increased Ag-specific production of the mast cell-activating cytokine IL-9. Our combined results support a model whereby BTLA on CD4(+) T cells and additional innate leukocytes is triggered by HVEM and delivers negative signals into BTLA(+) cells, thereby interfering with the protective immune response to this intestinal parasite.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany; and breloer@bnitm.de.
authors.forename: Minka
authors.initials: M
authors.lastname: Breloer
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany; and.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Hartmann
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany; and.
authors.forename: Birte
authors.initials: B
authors.lastname: Blankenhaus
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany; and.
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Eschbach
authors.affiliation: University Hospital Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfeffer
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany; and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018928:Immunity, Mucosal / Q000276:immunology*; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000276:immunology*; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D017170:Strongyloides ratti; D013322:Strongyloidiasis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: C488868:BTLA protein, mouse; D011971:Receptors, Immunologic; D053240:Receptors, Tumor Necrosis Factor, Member 14; C506029:Tnfrsf14 protein, mouse