title: Isoniazid treatment of Mycobacterium bovis in cattle as a model for human tuberculosis.
abstract: Cattle infected with Mycobacterium bovis spoligotype 9 were treated with Isoniazid (INH) from three to 14 weeks post infection, rested for fourweeks to allow INH depletion and then challenged with M. bovis spoligotype 35. Post mortem examination (PME) 35 weeks after the initial infection showed partial protection against infectious challenge following INH-attenuated infection compared with the spoligotype 35 challenge controls. Antigen-specific IFN-gamma responses decreased over time with INH therapy, following a similar pattern to that observed in the treatment of M. tuberculosis infection in humans. Following cessation of therapy, specific IFN-gamma responses increased more strongly in those calves that were visibly lesioned at PME. IFN-gamma responses were also used to identify two antigens, TB10.4 and Acr2, that induced anamnestic responses in INH-treated, re-challenged calves, suggesting a role for both antigens in protective immunity. Specific IL-10 responses were observed in all calves following treatment with INH suggesting a role for IL-10 in the resolution of infection.
authors.affiliation: TB Research Group, Veterinary Laboratories Agency, Woodham Lane, Weybridge, KT15 3NB, UK. g.dean@vla.defra.gsi.gov.uk
authors.forename: G S
authors.initials: GS
authors.lastname: Dean
authors.forename: S G
authors.initials: SG
authors.lastname: Rhodes
authors.forename: M
authors.initials: M
authors.lastname: Coad
authors.forename: A O
authors.initials: AO
authors.lastname: Whelan
authors.forename: P
authors.initials: P
authors.lastname: Wheeler
authors.forename: B
authors.initials: B
authors.lastname: Villareal-Ramos
authors.forename: E
authors.initials: E
authors.lastname: Mead
authors.forename: L
authors.initials: L
authors.lastname: Johnson
authors.forename: D J
authors.initials: DJ
authors.lastname: Clifford
authors.forename: R G
authors.initials: RG
authors.lastname: Hewinson
authors.forename: H M
authors.initials: HM
authors.lastname: Vordermeier
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D000995:Antitubercular Agents / Q000627:therapeutic use*; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology; D016207:Cytokines; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D007538:Isoniazid / Q000627:therapeutic use*; D008297:Male; D018598:Minisatellite Repeats; D009163:Mycobacterium bovis / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D011897:Random Allocation; D014374:Tuberculin Test; D014380:Tuberculosis, Bovine / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D000995:Antitubercular Agents; D016207:Cytokines; D016753:Interleukin-10; D007371:Interferon-gamma; D007538:Isoniazid