Correlation between augmented resistance to influenza virus infection and histological changes in lung of mice treated with trehalose-6,6'-dimycolate.

Mice inoculated intravenously with trehalose-6,6'-dimycolate (TDM), a glycolipid component of the cell wall of Mycobacterium, in an oil-in-water emulsion (TDM emulsion) acquired a high resistance to intranasal infection by influenza virus. Athymic nude mice inoculated with TDM emulsion could not acquire such an augmented resistance to influenza virus infection. The augmented antiviral resistance of TDM emulsion-treated mice was diminished by prior intravenous inoculation of silica particles, which selectively impair macrophage functions. In vitro experiments showed that macrophage cultures treated with TDM emulsion released an activator(s) of T lymphocytes. Histological studies of the lung of TDM emulsion-inoculated mice revealed that a typical granuloma and severe perivascular lymphocyte infiltration appeared, though no such histological change was observed in the lung of control emulsion-inoculated mice. The lungs from TDM emulsion-treated athymic nude mice and the lungs from silica particle- and TDM emulsion-treated mice showed fewer and smaller granulomata and milder perivascular lymphocyte infiltration than a typical granuloma and lymphocyte infiltration in the lungs of TDM emulsion-treated mice. These and earlier results suggest that an acquired antiviral resistance of TDM emulsion-treated mice was caused by elicitation of macrophages with TDM, then activation of T lymphocytes, leading to granuloma formation and an amplified earlier interferon production in response to influenza virus infection.