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Infection and Immunity, June 2002, p. 3020-3025, Vol. 70, No. 6
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.6.3020-3025.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

Francine Bouchonnet, Neio Boechat, Marcel Bonay,,{dagger} and Allan J. Hance*

INSERM U552, Faculté de Médecine Xavier Bichat, Paris, France

Received 9 November 2001/ Returned for modification 21 December 2001/ Accepted 11 March 2002

Administration of alpha/beta interferon (IFN-{alpha}/ß) to mice infected with Mycobacterium tuberculosis has been shown to increase mycobacterial growth. Because IFN-{alpha}/ß has direct pleiotropic effects on the differentiation and functional activities of macrophages, we evaluated the effect of IFN-{alpha}/ß 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-ß 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}/ß could directly promote mycobacterial growth in patients harboring these organisms.

* Corresponding author. Mailing address: INSERM U552, IMEA—INSERM, 46, rue Henri Huchard, 75018 Paris, France. Phone: 33-1-40-25-63-55. Fax: 33-1-40-25-63-70. E-mail: hance{at}bichat.inserm.fr.

Editor: S. H. E. Kaufmann

{dagger} Present address: Service de Physiologie—Explorations Fonctionnelles, Hôpital Bichat—Claude Bernard, Paris, France.

Infection and Immunity, June 2002, p. 3020-3025, Vol. 70, No. 6
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.6.3020-3025.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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