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Infection and Immunity, December 2001, p. 7262-7270, Vol. 69, No. 12
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 (M
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
). Host cells have developed different
mycobactericidal mechanisms, including the production of inflammatory
cytokines. The aim of this study was to compare the M
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 M
activation, as shown by reverse transcription-PCR analysis of IL-1
,
IL-6, IL-10, transforming growth factor beta, tumor necrosis factor
alpha, and gamma interferon (IFN-
) transcripts. Interestingly, when
IFN-
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 M
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.
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