Interferon-gamma (IFN-γ) 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-γ 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-γ throughout the 8-week period, suggesting that the 3T3/IL-18 cells induced the resistance to MAC infection via IFN-γ 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.
Bibliographical noteFunding Information:
We would like to thank Drs. D.S. Lim, H.Y. Chung, P. Gangadharam for providing valuable reagents. This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (03-PJ1-PG10-22000-0002).
Copyright 2017 Elsevier B.V., All rights reserved.
- IL-18-secreting fibroblast
- Mycobacterium avium
ASJC Scopus subject areas
- Molecular Medicine
- General Immunology and Microbiology
- General Veterinary
- Public Health, Environmental and Occupational Health
- Infectious Diseases