The fibroblast growth factor-2 arrests Mycobacterium avium sp. paratuberculosis growth and immunomodulates host response in macrophages.

Mycobacterium tuberculosisis (M. tb) epidemic is one of the most severe health problem worldwide, while mechanisms underlying its pathogenesis and host immune responses remain unclear. Mycobacterium avium (M. avium), a mycobacterial species related to M. tb, shares similarities with M. tb in many ways. In this study, using M. avium infection of macrophages as a model, we systematically studied the effect of fibroblast growth factor-2 (FGF-2) on M. avium infection of macrophages. Our results showed that M. avium infection could increase FGF-2 expression on both mRNA and protein levels. M. avium infection elevated TNF-α and IFN-γ production while the addition of FGF-2 could further increase TNF-α but not IFN-γ level. M. avium infection could increase the expression of oxygen/nitrogen metabolism proteins iNOS and SOD-1, and FGF-2 had additive effect on the expression of these two proteins. M. avium infection had inhibitive effect on actin expression while FGF-2 could partly counteract such inhibition. Moreover, FGF-2 could inhibit M. avium proliferation in macrophages. Our results together indicate that macrophage-secreted FGF-2 upon M. avium infection could suppress M. avium proliferation through various ways including cytokine production, enhancement of phagocytosis as well as oxygen/nitrogen metabolism.