title: Antigen-Specific Mammary Inflammation Depends on the Production of IL-17A and IFN-γ by Bovine CD4+ T Lymphocytes.
abstract: Intramammary infusion of the antigen used to sensitize cows by the systemic route induces a local inflammation associated with neutrophil recruitment. We hypothesize that this form of delayed type hypersensitivity, which may occur naturally during infections or could be induced intentionally by vaccination, can impact the outcome of mammary gland infections. We immunized cows with ovalbumin to identify immunological correlates of antigen-specific mammary inflammation. Intraluminal injection of ovalbumin induced a mastitis characterized by a prompt tissue reaction (increase in teat wall thickness) and an intense influx of leukocytes into milk of 10 responder cows out of 14 immunized animals. The magnitude of the local inflammatory reaction, assessed through milk leukocytosis, correlated with antibody titers, skin thickness test, and production of IL-17A and IFN-γ in a whole-blood antigen stimulation assay (WBA). The production of these two cytokines significantly correlated with the magnitude of the milk leukocytosis following the ovalbumin intramammary challenge. The IL-17A and IFN-γ production in the WBA was dependent on the presence of CD4+ cells in blood samples. In vitro stimulation of peripheral blood lymphocytes with ovalbumin followed by stimulation with PMA/ionomycin allowed the identification by flow cytometry of CD4+ T cells producing either IL-17A, IFN-γ, or both cytokines. The results indicate that the antigen-specific WBA, and specifically IL-17A and IFN-γ production by circulating CD4+ cells, can be used as a predictor of mammary hypersensitivity to protein antigens. This prompts further studies aiming at determining how Th17 and/or Th1 lymphocytes modulate the immune response of the mammary gland to infection.
authors.affiliation: UMR1282, Infectiologie et Santé Publique, INRA, Nouzilly, France; Université François Rabelais de Tours, Tours, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Rainard
authors.affiliation: UMR1282, Infectiologie et Santé Publique, INRA, Nouzilly, France; Université François Rabelais de Tours, Tours, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Cunha
authors.affiliation: UMR1282, Infectiologie et Santé Publique, INRA, Nouzilly, France; Université François Rabelais de Tours, Tours, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Ledresseur
authors.affiliation: UE1297, Unité Expérimentale de Physiologie Animale, UEPAO, INRA, Nouzilly, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Staub
authors.affiliation: Université François Rabelais de Tours, Tours, France; UMR0085, Physiologie de la Reproduction et du Comportement, INRA, Nouzilly, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Touzé
authors.affiliation: UMR1282, Infectiologie et Santé Publique, INRA, Nouzilly, France; Université François Rabelais de Tours, Tours, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Kempf
authors.affiliation: UMR1282, Infectiologie et Santé Publique, INRA, Nouzilly, France; Université François Rabelais de Tours, Tours, France.
authors.forename: Florence B
authors.initials: FB
authors.lastname: Gilbert
authors.affiliation: INP, ENVT, Université de Toulouse, Toulouse, France; UMR1225, Interactions Hôte Agents Pathogènes, INRA, Toulouse, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Foucras
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002417:Cattle; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007114:Immunization; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008413:Mastitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008892:Milk / Q000737:chemistry; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D012882:Skin Tests
chemical_list: D020381:Interleukin-17; D007371:Interferon-gamma; D010047:Ovalbumin