title: Suppression of ovine lymphocyte activation by Teladorsagia circumcincta larval excretory-secretory products.
abstract: Teladorsagia circumcincta is an important pathogenic nematode of sheep. It has been demonstrated previously that stimulation of murine T lymphocytes with excretory-secretory (ES) products derived from fourth stage larvae of T. circumcincta (Tci-L4-ES) results in de novo expression of Foxp3, a transcription factor intimately involved in regulatory T cell function. In the current study, Foxp3⁺ T cell responses in the abomasum and the effects of Tci-L4-ES on ovine peripheral blood mononuclear cells (PBMC) following T. circumcincta infection were investigated. T. circumcincta infection resulted in a significant increase in numbers of abomasal Foxp3⁺ T cells, but not an increase in the proportion of T cells expressing Foxp3. Unlike in mice, Tci-L4-ES was incapable of inducing T cell Foxp3 expression but instead suppressed mitogen-induced and antigen-specific activation and proliferation of ovine PBMC in vitro. This effect was heat labile, suggesting that it is mediated by protein(s). Suppression was associated with up-regulation of interleukin-10 (IL-10) mRNA, and specific monoclonal antibody neutralisation of IL-10 resulted in a 50% reduction in suppression, indicating involvement of the IL-10 signaling pathway. Suppression was significantly reduced in PBMC isolated from T. circumcincta infected vs. helminth-naïve lambs, and this reduction in suppression was associated with an increase in Tci-L4-ES antigen-specific T cells within the PBMC. In conclusion, we have identified a mechanism by which T. circumcincta may modulate the host adaptive immune response, potentially assisting survival of the parasite within the host. However, the impact of Tci-L4-ES-mediated lymphocyte suppression during T. circumcincta infection remains to be determined.
authors: Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, UK. Tom.McNeilly@moredun.ac.uk.
authors: Tom N
authors: TN
authors: McNeilly
authors: Mara
authors: M
authors: Rocchi
authors: Yvonne
authors: Y
authors: Bartley
authors: Jeremy K
authors: JK
authors: Brown
authors: David
authors: D
authors: Frew
authors: Cassandra
authors: C
authors: Longhi
authors: Louise
authors: L
authors: McLean
authors: Jenni
authors: J
authors: McIntyre
authors: Alasdair J
authors: AJ
authors: Nisbet
authors: Sean
authors: S
authors: Wattegedera
authors: John F
authors: JF
authors: Huntley
authors: Jacqueline B
authors: JB
authors: Matthews
mesh_terms: D000018:Abomasum / Q000276:immunology; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology; D007814:Larva / Q000254:growth & development / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D012756:Sheep; D012757:Sheep Diseases / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D014251:Trichostrongyloidea / Q000254:growth & development / Q000276:immunology*; D014252:Trichostrongyloidiasis / Q000235:genetics / Q000276:immunology / Q000469:parasitology / Q000662:veterinary*
chemical_list: D000947:Antigens, Helminth; D051858:Forkhead Transcription Factors; D016753:Interleukin-10
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