結核性肉芽腫炎症の制御における宿主遺伝子の役割

抄録

Natural bactericidal resistance of Mycobacterium bovis BCG is under the control of a single gene, Bcg. The development of lung granulomas in susceptible (Bcg^s) and resistant (Bcg^r) mice was studied in two sets of Bcg-congenic systems, the BALB/c (Bcg^s) -C.D2 (BALB/c.Bcg^r) pair and the B10. A (Bcg^s) -B10. A^r (Bcg^r) 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 Bcg^s mice. By contrast, minimal lesions were produced in Bcg^r mice given BCG or dextran beads. Aqueous extracts prepared from pulmonary granuloma lesions induced in Bcg^s 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 Bcg^r mice challenged with BCG and dextran beads. The activity of IL-1 was correlated with activity/size of the granulomatous inflammation in mice.
These results incucate that the Bcg 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.