Induction of in vivo resistance to Mycobacterium avium infection by intramuscular injection with DNA encoding interleukin-18.
Interferon-gamma (IFN-gamma) is closely associated with the generation of cell-mediated immunity and resistance to intracellular parasites. Interleukin-18 (IL-18) was known to strongly induce IFN-gamma production by T cells and natural killer (NK) cells. In order to determine whether injection with DNA encoding IL-18 can stimulate the resistance to Mycobacterium avium complex (MAC) infection, the mature IL-18 cDNA with kappa leader sequence was cloned under control of the cytomegalovirus (CMV) promoter (TcCMVIL-18) and its effect on MAC infection was investigated in genetically susceptible BALB/c mice. Injection with the TcCMVIL-18 DNA during intranasal infection with MAC resulted in a significant decrease in bacterial load of lung during the entire 8-week observation period, while injection with the TcCMV control DNA did not. Lung cells in mice injected with the TcCMVIL-18 DNA showed persistent production of IFN-gamma throughout the 8-week period. Furthermore, immunization with the TcCMVIL-18 DNA induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by lung cells than immunization with the TcCMV control vector. This work suggests that IL-18 DNA vaccination may be useful in the immunotherapeutic or immunoprotection approaches of infections by intracellular parasites such as mycobacteria.
College of Pharmacy, Chonnam National University, Kwangju, and Cancer Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009164:Mycobacterium Infections / Q000276:immunology / Q000517:prevention & control*; D009162:Mycobacterium avium / Q000254:growth & development / Q000276:immunology*; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001428:Bacterial Vaccines; D018076:DNA, Complementary; D020382:Interleukin-18; D019444:Vaccines, DNA; D007371:Interferon-gamma