A specific induction of interleukin-10 by the Map41 recombinant PPE antigen of Mycobacterium avium subsp. paratuberculosis

Interleukin-10 (IL-10) is not only an essential immunoregulator in host immunity, but also it accounts for the intracellular survival of mycobacteria because of its inhibitory activity against anti-mycobacterial functions of macrophage. It has been also indicated that blood cells from calves infected with Mycobacterium avium subsp. paratuberculosis (Map) produce a large amount of IL-10 after stimulation with Map antigen, and it leads to suppression of Interferon-gamma (IFN-γ) production in T-cells. This characteristic expression of IL-10 in Map-infected cattle seems to be playing important roles in the pathogenesis of Johneʹs disease caused by Map, and could be an important diagnostic indicator. The aim of this study was to investigate the diagnostic significance of IL-10 production from blood cells stimulated by a PPE (Proline–Proline–Glutamic acid) protein family of Map. The recombinant PPE protein, Map41, which has been reported as one of the IFN-γ inducing antigens of Map, also strongly induced IL-10 from macrophages obtained from infected calves. The elicited IL-10 production in response to Map41 from experimentally infected calves was as early as 2 weeks after the inoculation of Map, and the IL-10 production was detected earlier than that of IFN-γ. The blood cells from calves immunized with Map produced higher amounts of IL-10 against Map41 stimulation than those of calves immunized with various Mycobacterium species. Furthermore, this IL-10 induction also showed high specificity to Map in guinea pigs experimentally infected with various Mycobacterium species. These observations suggest that IL-10 assay is a useful diagnostic method in the early stage of Johneʹs disease.