Induction of in vivo resistance to Mycobacterium avium infection by intramuscular injection with DNA encoding interleukin-18

Immunology. 2001 Feb;102(2):234-41. doi: 10.1046/j.1365-2567.2001.01150.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Bacterial Vaccines / immunology*
  • DNA, Complementary / genetics
  • Female
  • Injections, Intramuscular
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-18 / genetics
  • Interleukin-18 / immunology*
  • Lung / immunology
  • Lung / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium Infections / immunology
  • Mycobacterium Infections / prevention & control*
  • Mycobacterium avium / growth & development
  • Mycobacterium avium / immunology*
  • Transfection
  • Vaccines, DNA / immunology*

Substances

  • Antibodies, Monoclonal
  • Bacterial Vaccines
  • DNA, Complementary
  • Interleukin-18
  • Vaccines, DNA
  • Interferon-gamma