Repeat tuberculin skin testing leads to desensitisation in naturally infected tuberculous cattle which is associated with elevated interleukin-10 and decreased interleukin-1 beta responses.
The principal surveillance tool used to control bovine tuberculosis in cattle is the removal of animals that provide a positive response to the tuberculin skin-test. In this study we performed a longitudinal investigation of the immunological and diagnostic consequences of repeated short-interval skin-tests in cattle naturally infected with Mycobacterium bovis. Tuberculin skin-test positive cattle were subjected to up to four further intradermal comparative cervical skin-tests at approximately 60-day intervals. A significant progressive reduction in the strength of the skin-test was observed after successive tests. In contrast, the magnitude of interferon-gamma (IFN-gamma) responses was not influenced by repeat skin-testing either transiently around the time of each skin-test or longitudinally following repeated tests. A significant boost in blood interleukin-10 (IL-10) production was observed within 3 days following each skin-test although the magnitude of this boosted response returned to lower levels by day 10 post-test. The application of a novel multiplex assay to simultaneously measure seven cytokines and chemokines also identified that skin-testing resulted in a significant and progressive reduction in antigen specific interleukin-1beta (IL-1beta) whilst confirming stable IFN-gamma and elevated IL-10 responses in the blood. Therefore, we have demonstrated that in cattle naturally infected with M. bovis, repeat short-interval skin-testing can lead to a progressive reduction in skin-test responsiveness which has potential negative consequences for the detection of infected animals with marginal or inconclusive skin-test responses. The desensitising effect is associated with decreased IL-1beta and elevated IL-10 responses, but importantly, does not influence antigen specific IFN-gamma responses.
TB Research Group, Veterinary Laboratories Agency, Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, United Kingdom. m.coad@vla.defra.gsi.gov.uk
Michael
M
Coad
Derek
D
Clifford
Shelley G
SG
Rhodes
R Glyn
RG
Hewinson
H Martin
HM
Vordermeier
Adam O
AO
Whelan
D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000175:diagnosis / Q000378:metabolism*; D003888:Desensitization, Immunologic / Q000662:veterinary*; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood / Q000378:metabolism*; D053583:Interleukin-1beta / Q000097:blood / Q000378:metabolism*; D013997:Time Factors; D014374:Tuberculin Test / Q000662:veterinary*; D014376:Tuberculosis / Q000175:diagnosis / Q000378:metabolism / Q000662:veterinary*
D053583:Interleukin-1beta; D016753:Interleukin-10; D007371:Interferon-gamma