Role of Interferon in the Augmented Resistance of Trehalose-6,6'-dimycolate-treated Mice to Influenza Virus Infection

Mice inoculated intravenously with 10 to 100 micrograms trehalose-6,6'-dimycolate in an oil-in-water emulsion (TDM emulsion) acquired high resistance to intranasal infection by influenza virus at 7 to 14 days, but not at 1 day, after treatment. Mice inoculated with an oil-in-water emulsion without TDM (control emulsion) did not resist infection. The activity of the reticuloendothelial system of mice inoculated with TDM emulsion or control emulsion was greatly stimulated 1 day and 14 days after treatment. Interferon production in response to influenza virus was augmented in lung and serum of TDM emulsion-treated mice. The augmented interferon production was greatly diminished in the TDM emulsion-treated mice by treatment with anti-Thy-1.2 monoclonal antibody. Production of haemagglutination-inhibiting antibody in the TDM emulsion-treated or control emulsion-treated mice was higher than that in untreated mice, although no difference was observed between the TDM emulsion-treated and control emulsion-treated mice. On the other hand, TDM emulsion treatment of mice did not influence the appearance of antibody-producing cells, nor the activity of natural killer cells in the mice. The enhanced resistance of mice was diminished by inoculating anti-interferon-alpha/beta serum before influenza virus infection. No detectable interferon activity was observed in lung and blood of mice inoculated with anti-interferon-alpha/beta serum prior to influenza virus infection. These results suggest that the augmented early interferon production in T-lymphocytes of TDM emulsion-treated mice in response to influenza virus may play an important role in the enhanced resistance.