Induction of persistent in vivo resistance to Mycobacterium avium infection in BALB/c mice injected with interleukin-18-secreting fibroblasts.
Interferon-gamma (IFN-gamma) is closely associated with the generation of cell-mediated immunity and resistance to intracellular parasites. Interleukin-18 (IL-18) is known to strongly induce IFN-gamma production by T cells and natural killer (NK) cells. To determine whether the paracrine secretion of IL-18 can efficiently stimulate the resistance to Mycobacterium avium complex (MAC) infection, 3T3 fibroblasts were stably transfected to secrete bioactive IL-18 and their effects on MAC infection were investigated in genetically susceptible BALB/c mice, compared with that of free recombinant IL-18. Immunization with IL-18-secreting fibroblasts (3T3/IL-18) during intranasal infection with MAC resulted in a significant decrease in bacterial load of lung during the entire 8-week observation period, while rIL-18 reduced the bacterial load at initial 1 week but not by 8 weeks postinfection. Immunization with the 3T3/IL-18 cells induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by lung cells than those of rIL-18 immunization. Furthermore, lung cells in mice injected with the 3T3/IL-18 cells showed persistent production of IFN-gamma throughout the 8-week period, suggesting that the 3T3/IL-18 cells induced the resistance to MAC infection via IFN-gamma production. This work suggests that IL-18-secreting fibroblasts may serve as a vehicle for paracrine secretion of IL-18 in immunotherapy of MAC infection.
Chung
Su W
SW
Department of Pharmacy, College of Pharmacy, Chonnam National University, 500-757 Kwangju, Republic of Korea.
Choi
Sang H
SH
Kim
Tae S
TS
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000494:pharmacology; D015153:Blotting, Western; D016207:Cytokines / Q000096:biosynthesis; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics; D007202:Indicators and Reagents; D007371:Interferon-gamma / Q000276:immunology; D020382:Interleukin-18 / Q000378:metabolism*; D008168:Lung / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D015269:Mycobacterium avium Complex / Q000276:immunology*; D015270:Mycobacterium avium-intracellulare Infection / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014162:Transfection
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007202:Indicators and Reagents; D020382:Interleukin-18; D009569:Nitric Oxide; D007371:Interferon-gamma