Comparative ability of human monocytes and macrophages to control the intracellular growth ofMycobacterium aviumandMycobacterium tuberculosis: effect of interferon-gamma and indomethacin

Abstract

Intracellular growth of Mycobacterium avium and M. tuberculosis H37Rv was compared both in human peripheral blood monocytes and in cultured macrophages. The cells were treated with 300 U of human recombinant interferon-gamma (IFN gamma) either 48 h prior to phagocytosis or after infection. In some cases, indomethacin (IND, a potent inhibitor of prostaglandin-E2 synthesis), was added immediately after infection of macrophages. IFN gamma pretreatment of monocytes resulted in about 50% lesser uptake of both pathogens, but had no effect in macrophages. Macrophages, as compared to monocytes, were more permissive to M. avium growth suggesting that monocytes may be innately more efficient in controlling the intracellular growth of this pathogen. About ten-fold higher growth of M. avium as compared to M. tuberculosis was observed in both culture systems. IFN gamma-treatment alone did not confer any anti-M. avium activity to monocytes and macrophages alike and addition of IND did not change this unresponsiveness. In the case of M. tuberculosis, the IFN gamma treatment alone endowed both monocytes and macrophages with significant bacteriostatic activity which was further potentiated by the addition of IND. These observations show innate differences in the ability of human monocytes and macrophages to control the growth of two major mycobacterial pathogens and the immunoregulatory mechanisms involved.