title: Increased blood-circulating interferon-γ, interleukin-17, and osteopontin levels in bovine paratuberculosis.
abstract: Paratuberculosis-infected cattle initially develop an effective cell-mediated immune response that declines as the disease progresses. Blood is one of best sources for characterizing the inflammatory status of infected cows and for studying mediators related to chronic diseases. The aim of this study was to evaluate the cow-level association between blood cytokine concentration, the influence of serum on immune cell proliferation, and dairy cows naturally infected with Mycobacterium avium ssp. paratuberculosis (MAP). Positive animals (n=41) from 19 herds were selected on the basis of 2 positive fecal culture results and divided into 2 groups: single-positive, or serum ELISA-negative cows (n=32), and double-positive, or cows that gave positive results for both mycobacterial culture and serum ELISA (n=9). Negative animals (n=39) were selected from paratuberculosis-negative herds in which at least 80% of the animals had been diagnosed as negative by fecal culture and ELISA and that did not produce positive results during the 2-yr study. Analysis of plasma levels of the cytokines IL-4, IL-10, IL-17, IFN-γ, and osteopontin was performed, revealing distinct patterns. The ELISA-positive cows with MAP shedding had similar plasma concentrations of IL-4 and IL-10 but elevated levels of IFN-γ, IL-17, and osteopontin, which is indicative of inflammatory disease in these subclinical positive cows. In vitro MAP infection of bovine macrophages showed increased gene expression of tumor necrosis factor-α, IL-1β, IL-6, IL-23, and transforming growth factor-β as early as 6h postinfection for all of the cytokines involved in the establishment of a T-helper type-17 immune response. To determine the systemic influence of serum on immune cell functions, lymphoproliferation assays were also performed in presence of JD serum. The serum from shedding cows showed 15% less proliferation. These results indicate that infected cows have a lower systemic capacity to maintain a protective immune response and that, as the disease progresses, an emerging T-helper type-17 immune response is established.
authors.affiliation: Dairy and Swine Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, QC, Canada J1M 1Z3; Département de biochimie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, QC, Canada J1H 5N4.
authors.forename: P L
authors.initials: PL
authors.lastname: Dudemaine
authors.affiliation: Faculté de médecine vétérinaire, Université de Montréal, Saint-Hyacinthe, QC, Canada J2S 2M2.
authors.forename: G
authors.initials: G
authors.lastname: Fecteau
authors.affiliation: Dairy and Swine Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, QC, Canada J1M 1Z3.
authors.forename: M
authors.initials: M
authors.lastname: Lessard
authors.affiliation: Laboratoire d'épidémiosurveillance animale du Québec, Ministère de l'agriculture, des pêcheries et de l'alimentation du Québec, Québec, Saint-Hyacinthe, QC, Canada J2S 7X9.
authors.forename: O
authors.initials: O
authors.lastname: Labrecque
authors.affiliation: Faculté de médecine vétérinaire, Université de Montréal, Saint-Hyacinthe, QC, Canada J2S 2M2.
authors.forename: J P
authors.initials: JP
authors.lastname: Roy
authors.affiliation: Dairy and Swine Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, QC, Canada J1M 1Z3; Département de biochimie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, QC, Canada J1H 5N4. Electronic address: nathalie.bissonnette@agr.gc.ca.
authors.forename: N
authors.initials: N
authors.lastname: Bissonnette
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000097:blood / Q000382:microbiology*; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D005260:Female; D015870:Gene Expression; D007371:Interferon-gamma / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood; D020381:Interleukin-17 / Q000097:blood*; D053583:Interleukin-1beta / Q000378:metabolism; D053759:Interleukin-23 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008264:Macrophages / Q000378:metabolism; D016927:Mycobacterium avium subsp. paratuberculosis / Q000302:isolation & purification; D053495:Osteopontin / Q000097:blood*; D010283:Paratuberculosis / Q000097:blood / Q000382:microbiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D053495:Osteopontin; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: bovine paratuberculosis; cell proliferation; interleukin-17; osteopontin