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Laboratoire de Microbiologie Génétique et Moléculaire Institut National de la Santé et de la Recherche Médicale U447,
Centre d’Immunologie et de Biologie Parasitaire, Institut National de la Santé et de la Recherche Médicale U167, and
Centre National de la Recherche Scientifique Unité de Recherche Associée 1854, Institut Pasteur de Lille, Lille, France
IL-18, a recently identified cytokine synthesized by different cell
types, including Kupffer cells, activated macrophages, and
keratinocytes, induces IFN-
production by T cells and NK cells. The
cDNA encoding IL-18 with its natural signal peptide was cloned under
control of the CMV promoter and injected into the skin of mice. A
single intradermal injection of this construction led to efficient in
vivo expression of IL-18 in cutaneous dermal cells and induced IFN-
mRNA production, indicating that it was produced in a biologically
active form. In addition, a massive cellular infiltrate was observed in
the skin 2 days after injection. When the mice were subsequently
infected with Mycobacterium bovis bacillus
Calmette-Guérin (BCG), they produced lower levels of anti-BCG
Abs than control animals. However, in contrast to their lowered humoral
immune response, the mice produced higher amounts of Ag-specific
IFN- after in vitro restimulation, as compared with the controls.
Therefore, injection of DNA encoding IL-18 into the skin modulates both
Ag-specific humoral and T cell responses upon mycobacterial infection.
It increases the Th1 type response, which may be particularly useful
for the development of new immunotherapeutic or immunoprotective
approaches against infections by intracellular parasites, such as
mycobacteria.
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