Isoniazid treatment of Mycobacterium bovis in cattle as a model for human tuberculosis

G. S. Dean*, S. G. Rhodes, M. Coad, A. O. Whelan, P. Wheeler, B. Villareal-Ramos, E. Mead, L. Johnson, D. J. Clifford, R. G. Hewinson, H. M. Vordermeier

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Citations (SciVal)

Abstract

Cattle infected with Mycobacterium bovis spoligotype 9 were treated with Isoniazid (INH) from three to 14 weeks post infection, rested for four weeks 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-γ 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-γ responses increased more strongly in those calves that were visibly lesioned at PME. IFN-γ 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. Crown

Original languageEnglish
Pages (from-to)586-594
Number of pages9
JournalTuberculosis
Volume88
Issue number6
Early online date02 May 2008
DOIs
Publication statusPublished - 01 Nov 2008

Keywords

  • Drug-induced
  • Protection
  • Tuberculosis

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