Effects of Gamma Interferon, Interleukin-10, and Transforming Growth Factor β on the Survival of Mycobacterium aviumsubsp. paratuberculosisin Monocyte-Derived Macrophages from Naturally Infected Cattle

ABSTRACTGamma interferon (IFN-γ) plays a significant role in the control of mycobacterial infections, including Mycobacterium aviumsubsp. paratuberculosis. However, the contribution of other immunoregulatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor β (TGF-β), in Johne's disease has not been investigated as yet. In this study, we examined the effects of in vivo and in vitro infection with M. aviumsubsp. paratuberculosison the production of IFN-γ, IL-10, and TGF-β by peripheral blood mononuclear cells (PBMC). We also examined the effects of exogenous IFN-γ, IL-10, and TGF-β on M. aviumsubsp. paratuberculosissurvival in the cell cultures. PBMC obtained from naturally infected cows, regardless of their disease status, specifically upregulated IL-10 and TGF-β in culture supernatants in response to stimulation with live M. aviumsubsp. paratuberculosis. Nonstimulated PBMC recovered from subclinically infected animals secreted the lowest levels of TGF-β, but after stimulation with live M. aviumsubsp. paratuberculosis, TGF-β levels in the culture supernatants increased to levels similar to that produced by PBMC from healthy animals. The numbers of viable M. aviumsubsp. paratuberculosisrecovered from cultures from naturally infected animals were higher than those from healthy cows after in vitro infection with M. aviumsubsp. paratuberculosis. The addition of exogenous IL-10 and TGF-β to PBMC isolated from healthy cows inhibited the bactericidal activity of these cells as evidenced by the increased number of viable M. aviumsubsp. paratuberculosisrecovered from these cultures compared to cell cultures containing medium alone. These data suggest important immune regulatory roles for IL-10 and TGF-β during infection with M. aviumsubsp. paratuberculosisthat may be directly related to their effects on macrophage activation and killing of M. aviumsubsp. paratuberculosis.