Induction of in vivo persistent anti-mycobacterial activity by interferon-γ-secreting fibroblasts

Abstract

To determine whether the paracrine secretion of interferon-γ (IFN-γ) can efficiently stimulate the resistance to Mycobacterium avium complex (MAC) infection, 3T3 fibroblasts were stably transduced to secrete IFN-γ (500 units/106 cells/48 h) and their effects on MAC infection were investigated in genetically susceptible BALB/c mice, compared with that of free recombinant IFN-γ (rIFN-γ). Immunization with IFN-γ-secreting fibroblasts (3T3-IFN-γ) during intranasal infection with MAC resulted in a significant decrease in bacterial load of lung during the entire 8-week observation period, while rIFN-γ reduced the bacterial load at initial 1 week but not by 8 weeks postinfection. Furthermore, immunization with the 3T3-IFN-γ cells induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by lung cells than those of rIFN-γ immunization. This work suggest that IFN-γ-secreting fibroblasts may serve as a vehicle for paracrine secretion of IFN-γ in immunotherapy of MAC infection.