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.
Kim
S H
SH
College of Pharmacy, Chonnam National University, Kwangju, and Cancer Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
Cho
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Kim
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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