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Infection and Immunity, December 2001, p. 7262-7270, Vol. 69, No. 12
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.12.7262-7270.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Human Macrophage Gamma Interferon Decreases Gene Expression but Not Replication of Mycobacterium tuberculosis: Analysis of the Host-Pathogen Reciprocal Influence on Transcription in a Comparison of Strains H37Rv and CMT97

Giulia Cappelli,1,2,3 Pietro Volpe,1,2 Alessandro Sanduzzi,4 Alessandra Sacchi,1,3 Vittorio Colizzi,2,3 and Francesca Mariani1,*

Department of Biology, University Tor Vergata,2 Institute of Neurobiology and Molecular Medicine, National Research Council,1 and International Centre for AIDS and Emerging and Reemerging Infections INMI-L.Spallanzani,3 Rome, and Department of Respiratory Medicine, University of Naples Federico II, Naples,4 Italy

Received 4 June 2001/Returned for modification 10 July 2001/Accepted 15 August 2001

Mycobacterium tuberculosis is an intracellular pathogen that readily survives and replicates in human macrophages (MPhi ). Host cells have developed different mycobactericidal mechanisms, including the production of inflammatory cytokines. The aim of this study was to compare the MPhi response, in terms of cytokine gene expression, to infection with the M. tuberculosis laboratory strain H37Rv and the clinical M. tuberculosis isolate CMT97. Both strains induce the production of interleukin-12 (IL-12) and IL-16 at comparable levels. However, the clinical isolate induces a significantly higher and more prolonged MPhi activation, as shown by reverse transcription-PCR analysis of IL-1beta , IL-6, IL-10, transforming growth factor beta, tumor necrosis factor alpha, and gamma interferon (IFN-gamma ) transcripts. Interestingly, when IFN-gamma transcription is high, the number of M. tuberculosis genes expressed decreases and vice versa, whereas no mycobactericidal effect was observed in terms of bacterial growth. Expression of 11 genes was also studied in the two M. tuberculosis strains by infecting resting or activated MPhi and compared to bacterial intracellular survival. In both cases, a peculiar inverse correlation between expression of these genes and multiplication was observed. The number and type of genes expressed by the two strains differed significantly.


* Corresponding author. Mailing address: Institute of Neurobiology and Molecular Medicine, National Research Council, Via Fosso del Cavaliere, 100, 00133 Rome, Italy. Phone: 39 06 4993 4206. Fax: 39 06 4993 4257. E-mail: Francesca.Mariani{at}ims.rm.cnr.it.


Infection and Immunity, December 2001, p. 7262-7270, Vol. 69, No. 12
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.12.7262-7270.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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