Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 2/6/2004
Publication Date: 4/17/2004
Citation: Stabel, J.R., Khalifeh, M.S. 2004. Effects of Interferon-g, Interleukin-10, and Transforming growth factor-b on survival of Mycobacterium paratuberculosis in Monocyte-derived Macrophages from naturally infected cattle [abstract]. Federation of American Societies for Experimental Biology Conference. p. 251. Interpretive Summary:
Technical Abstract: Interferon-g (IFN-g) plays a significant role in the control of mycobacterial infections, including Mycobacterium paratuberculosis. However, the contribution of other immunoregulatory cytokines such as interleukin-10 (IL-10) and transforming growth factor-b (TGF-b) in Johne's disease has not been investigated as yet. In the present study, we examined the effects of in vivo and in vitro infection with M. paratuberculosis on the production of IFN-g, IL-10 and TGF-b by peripheral blood mononuclear cells (PBMC). We also examined the effects of exogenous IFN-g, IL-10 and TGF-b on M. paratuberculosis survival in the cell cultures. PBMC obtained from naturally infected cows, regardless of their disease status, specifically upregulated IL-10 and TGF-b in culture supernatants in response to stimulation with live M. paratuberculosis. Non-stimulated PBMC recovered from subclinically infected animals secreted the lowest levels of TGF-b but after stimulation with live M. paratuberculosis TGF-b levels in the culture supernatants increased to levels similar to that produced by PBMC from healthy animals. Compared to healthy cows, naturally infected animals had higher numbers of viable M. paratuberculosis recovered from their cultures after in vitro infection with M. paratuberculosis. The addition of exogenous IL-10 and TGF-b to PBMC isolated from healthy cows inhibited the bactericidal activity of these cells as evidenced by the increased number of viable M. paratuberculosis recovered from those cultures compared to cell cultures containing medium alone. These data suggest an important immune regulatory role of IL-10 and TGF-b during infection with M. paratuberculosis that may be directly related to their effects on macrophage activation and killing of M. paratuberculosis.