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,,
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-
/ß) to mice infected with Mycobacterium tuberculosis has been shown to increase mycobacterial growth. Because IFN-
/ß has direct pleiotropic effects on the differentiation and functional activities of macrophages, we evaluated the effect of IFN-
/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-
) 3 days prior to or concomitant with infection. This striking loss of mycobacteriostatic activity was observed with IFN-
and IFN-ß and was induced in both freshly isolated monocytes and culture-derived macrophages. Pretreatment of monocytes with IFN-
modified cellular morphology and reduced viability following culture, but neither was observed for culture-derived macrophages, indicating that the effects of IFN-
on mycobacteriostatic activity and cell differentiation and death could be dissociated. These results are compatible with the possibility that the secretion of IFN-
/ß could directly promote mycobacterial growth in patients harboring these organisms.
* Corresponding author. Mailing address: INSERM U552, IMEAINSERM, 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
Present address: Service de PhysiologieExplorations Fonctionnelles, Hôpital BichatClaude 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.
This article has been cited by other articles:
-
Pagliano, P., Costantini, S., Gradoni, L., Faella, F. S., Spasiano, A., Mascarella, G., Prossomariti, L., Fusco, U., Ricchi, P.
(2008). Distinguishing Visceral Leishmaniasis from Intolerance to Pegylated Interferon-{alpha} in a Thalassemic Splenectomized Patient Treated for Chronic Hepatitis C. Am J Trop Med Hyg
79: 9-11
[Abstract]
[Full Text]
-
Mancuso, G., Midiri, A., Biondo, C., Beninati, C., Zummo, S., Galbo, R., Tomasello, F., Gambuzza, M., Macri, G., Ruggeri, A., Leanderson, T., Teti, G.
(2007). Type I IFN Signaling Is Crucial for Host Resistance against Different Species of Pathogenic Bacteria. J. Immunol.
178: 3126-3133
[Abstract]
[Full Text]
-
Stanley, S. A., Johndrow, J. E., Manzanillo, P., Cox, J. S.
(2007). The Type I IFN Response to Infection with Mycobacterium tuberculosis Requires ESX-1-Mediated Secretion and Contributes to Pathogenesis. J. Immunol.
178: 3143-3152
[Abstract]
[Full Text]
-
Shi, S., Blumenthal, A., Hickey, C. M., Gandotra, S., Levy, D., Ehrt, S.
(2005). Expression of Many Immunologically Important Genes in Mycobacterium tuberculosis-Infected Macrophages Is Independent of Both TLR2 and TLR4 but Dependent on IFN-{alpha}{beta} Receptor and STAT1. J. Immunol.
175: 3318-3328
[Abstract]
[Full Text]
Copyright © 2002 by the American Society for Microbiology. All rights reserved.