title: Early immune markers associated with Mycobacterium avium subsp. paratuberculosis infection in a neonatal calf model.
abstract: The objective of this study was to observe early markers of cell-mediated immunity in naïve calves infected with Mycobacterium avium subsp. paratuberculosis and how expression of these markers evolved over the 12-month period of infection. Groups for experimental infection included control (noninfected), oral (infected orally with M. avium subsp. paratuberculosis strain K-10), oral/DXM (pretreatment with dexamethasone before oral inoculation), intraperitoneal (i.p.) inoculation, and oral/M (oral inoculation with mucosal scrapings from a cow with clinical disease) groups. One of the earliest markers to emerge was antigen-specific gamma interferon (IFN-γ). Only i.p. inoculated calves had detectable antigen-specific IFN-γ responses at 7 days, with responses of the other infection groups becoming detectable at 90 and 120 days. All infection groups maintained robust IFN-γ responses for the remainder of the study. At 1 month, calves in the oral and oral/M groups had higher antigen-stimulated interleukin-10 (IL-10) levels than calves in the other treatment groups, but IL-10 secretion declined by 12 months for all calves. T-cell activation markers such as CD25, CD26, CD45RO, and CD5 were significantly upregulated in infected calves compared to noninfected controls. Oral inoculation of calves resulted in significantly increased antigen-specific lymphocyte proliferation at 9 and 12 months, as well as inducible nitric oxide synthase (iNOS) secretion at 6 and 12 months. These results demonstrate that infection of naïve calves with M. avium subsp. paratuberculosis invoked early immunologic responses characterized by robust antigen-specific IFN-γ responses and induction of CD25 and CD45RO expression on T-cell subsets. These were followed by antigen-specific lymphocyte proliferation, iNOS secretion, and expression of CD26 and CD5(bright) markers in the latter part of the 12-month study.
authors.affiliation: USDA-ARS, National Animal Disease Center, 1920 Dayton Ave., Building 20, Ames, IA 50010, USA. judy.stabel@ars.usda.gov
authors.forename: J R
authors.initials: JR
authors.lastname: Stabel
authors.forename: S
authors.initials: S
authors.lastname: Robbe-Austerman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000032:analysis; D015415:Biomarkers; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000378:metabolism; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010283:Paratuberculosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II