Genetic regulation of tuberculous granulomatous inflammation.
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概要
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Natural bactericidal resistance of <I>Mycobacterium bovis</I> BCG is under the control of a single gene, <I>Bcg</I>. The development of lung granulomas in susceptible (<I>Bcg</I><SUP>s</SUP>) and resistant (<I>Bcg</I><SUP>r</SUP>) mice was studied in two sets of <I>Bcg</I>-congenic systems, the BALB/c (<I>Bcg</I><SUP>s</SUP>) -C.D2 (BALB/c.<I>Bcg</I><SUP>r</SUP>) pair and the B10. A (<I>Bcg</I><SUP>s</SUP>) -B10. A<SUP>r</SUP> (<I>Bcg</I><SUP>r</SUP>) pair, by using BCG as well as foregin-body granuloma-inducing agents, dextran beads. Large lung granulomas induced by the intratracheal challenge of either BCG or dextran beads developed in <I>Bcg</I><SUP>s</SUP> mice. By contrast, minimal lesions were produced in <I>Bcg</I><SUP>r</SUP> mice given BCG or dextran beads. Aqueous extracts prepared from pulmonary granuloma lesions induced in <I>Bcg</I><SUP>s</SUP> mice by either BCG or dextran beads contained a large amount of interleukin 1 (IL-1) activity but not IL-2 or IL-4 activity. Very low IL-1 activity was detectable in extracts from <I>Bcg</I><SUP>r</SUP> mice challenged with BCG and dextran beads. The activity of IL-1 was correlated with activity/size of the granulomatous inflammation in mice.<BR>These results incucate that the <I>Bcg</I> gene has pleiotropic effects on the development of granulomas induced by either BCG or nonspecific foreign body agents (dextran beads) and that macrophage-derived cytokines participate in granuloma formation.
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