Alpha/beta interferon impairs the ability of human macrophages to control growth of Mycobacterium bovis BCG.
Administration of alpha/beta interferon (IFN-alpha/beta) to mice infected with Mycobacterium tuberculosis has been shown to increase mycobacterial growth. Because IFN-alpha/beta has direct pleiotropic effects on the differentiation and functional activities of macrophages, we evaluated the effect of IFN-alpha/beta 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-alpha) 3 days prior to or concomitant with infection. This striking loss of mycobacteriostatic activity was observed with IFN-alpha and IFN-beta and was induced in both freshly isolated monocytes and culture-derived macrophages. Pretreatment of monocytes with IFN-alpha modified cellular morphology and reduced viability following culture, but neither was observed for culture-derived macrophages, indicating that the effects of IFN-alpha on mycobacteriostatic activity and cell differentiation and death could be dissociated. These results are compatible with the possibility that the secretion of IFN-alpha/beta could directly promote mycobacterial growth in patients harboring these organisms.
Bouchonnet
Francine
F
INSERM U552, Faculté de Médecine Xavier Bichat, Paris, France.
Boechat
Neio
N
Bonay
Marcel
M
Hance
Allan J
AJ
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology* / Q000494:pharmacology; D016899:Interferon-beta / Q000276:immunology* / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000382:microbiology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D009163:Mycobacterium bovis / Q000254:growth & development*; D013997:Time Factors
D016898:Interferon-alpha; D016899:Interferon-beta