Regulation of Mycobacterium bovis BCG and foreign body granulomas in mice by the Bcg gene

Abstract

Natural bactericidal resistance to Mycobacterium bovis BCG is under the control of a single gene, designated Bcg. Lung granuloma formation is suspectible (Bcg(s)) and resistant (Bcg(r)) mice was studied in two sets of Bcg-congenic systems, namely, 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 foreign body granuloma-inducing agent (dextran beads). Large granulomas of the lung induced by the intratracheal installation of either BCG or dextran beads developed in Bcg(s) mice. In contrast, minimal inflammation was 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 high levels of interleukin-1 (IL-1) activity but not interleukin-2 (IL-2) or interleukin-4 (IL-4) activity. Very low IL-1 activity was detected in extracts from Bcg(r) mice injected with BCG and dextran beads. The activity of IL-1 was correlated closely with the activity and size of the granulomatous inflammation in mice. These results suggest that pleiotropic effects of the Bcg gene are involved in the development of granulomas induced by either BCG or nonspecific foreign body agents (dextran beads) and that monokines participate in granuloma formation.