Alpha/Beta Interferon Impairs the Ability of Human Macrophages To Control Growth of Mycobacterium bovis BCG

Abstract

ABSTRACT Administration of alpha/beta interferon (IFN-α/β) to mice infected with Mycobacterium tuberculosis has been shown to increase mycobacterial growth. Because IFN-α/β has direct pleiotropic effects on the differentiation and functional activities of macrophages, we evaluated the effect of IFN-α/β on mycobacterial growth in human monocytes/macrophages in vitro. Monocytes cultured at optimal cell density could control the growth of M. bovis BCG, as assessed both by measurement of luciferase activity expressed by a mycobacterial reporter strain and by counting of CFU. In contrast, unrestrained mycobacterial growth was observed when monocytes were treated with alpha interferon (IFN-α) 3 days prior to or concomitant with infection. This striking loss of mycobacteriostatic activity was observed with IFN-α and IFN-β and was induced in both freshly isolated monocytes and culture-derived macrophages. Pretreatment of monocytes with IFN-α modified cellular morphology and reduced viability following culture, but neither was observed for culture-derived macrophages, indicating that the effects of IFN-α on mycobacteriostatic activity and cell differentiation and death could be dissociated. These results are compatible with the possibility that the secretion of IFN-α/β could directly promote mycobacterial growth in patients harboring these organisms.