title: Strongyloides ratti infection induces expansion of Foxp3+ regulatory T cells that interfere with immune response and parasite clearance in BALB/c mice.
abstract: To escape expulsion by their host's immune system, pathogenic nematodes exploit regulatory pathways that are intrinsic parts of the mammalian immune system, such as regulatory T cells (Tregs). Using depletion of Treg mice, we showed that Foxp3(+) Treg numbers increased rapidly during infection with the nematode Strongyloides ratti. Transient depletion of Tregs during the first days of infection led to dramatically reduced worm burden and larval output, without aggravation of immune pathology. The transient absence of Tregs during primary infection did not interfere with the generation of protective memory. Depletion of Tregs at later time points of infection (i.e., day 4) did not improve resistance, suggesting that Tregs exert their counterregulatory function during the priming of S. ratti-specific immune responses. Improved resistance upon early Treg depletion was accompanied by accelerated and prolonged mast cell activation and increased production of types 1 and 2 cytokines. In contrast, the blockade of the regulatory receptor CTLA-4 specifically increased nematode-specific type 2 cytokine production. Despite this improved immune response, resistance to the infection was only marginally improved. Taken together, we provide evidence that Treg expansion during S. ratti infection suppresses the protective immune response to this pathogenic nematode and, thus, represents a mechanism of immune evasion.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.
authors.forename: Birte
authors.initials: B
authors.lastname: Blankenhaus
authors.forename: Ulrike
authors.initials: U
authors.lastname: Klemm
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Eschbach
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.forename: Jochen
authors.initials: J
authors.lastname: Huehn
authors.forename: Anja A
authors.initials: AA
authors.lastname: Kühl
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.forename: Thomas
authors.initials: T
authors.lastname: Jacobs
authors.forename: Minka
authors.initials: M
authors.lastname: Breloer
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D060908:CTLA-4 Antigen; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D057131:Immune Evasion / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D008212:Lymphocyte Depletion; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D051381:Rats; D017208:Rats, Wistar; D017170:Strongyloides ratti / Q000276:immunology*; D013322:Strongyloidiasis / Q000276:immunology* / Q000469:parasitology / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000469:parasitology / Q000473:pathology*
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse