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Infection and Immunity, June 2006, p. 3296-3304, Vol. 74, No. 6
0019-9567/06/$08.00+0     doi:10.1128/IAI.01687-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Infection of Human Dendritic Cells with a Mycobacterium tuberculosis sigE Mutant Stimulates Production of High Levels of Interleukin-10 but Low Levels of CXCL10: Impact on the T-Cell Response

Elena Giacomini,1 Ambar Sotolongo,1 Elisabetta Iona,1 Martina Severa,1 Maria Elena Remoli,1 Valerie Gafa,1 Roberto Lande,1 Lanfranco Fattorini,1 Issar Smith,2 Riccardo Manganelli,3 and Eliana M. Coccia1*

Department of Infectious, Parasitic and Immuno-Mediated Diseases, Istituto Superiore di Sanità, Rome 00161, Italy,1 TB Center, Public Health Research Institute, Newark, New Jersey 07103,2 Department of Histology, Microbiology and Medical Biotechnologies, University of Padua, 35100 Padua, Italy3

Received 13 October 2005/ Returned for modification 29 November 2005/ Accepted 27 March 2006

The Mycobacterium tuberculosis genome encodes 13 sigma factors. We have previously shown that mutations in some of these transcriptional activators render M. tuberculosis sensitive to various environmental stresses and can attenuate the virulence phenotype. In this work, we focused on extracytoplasmic factor {sigma}E and studied the effects induced by the deletion of its structural gene (sigE) in the infection of human monocyte-derived dendritic cells (MDDC). We found that the wild-type M. tuberculosis strain (H37Rv), the sigE mutant (ST28), and the complemented strain (ST29) were able to infect dendritic cells (DC) to similar extents, although at 4 days postinfection a reduced ability to grow inside MDDC was observed for the sigE mutant ST28. After mycobacterium capture, the majority of MDDC underwent full maturation and expressed both inflammatory cytokines, such as tumor necrosis factor alpha, and the regulatory cytokines interleukin-12 (IL-12), IL-18, and beta interferon (IFN-ß). Conversely, a higher level of production of IL-10 was observed in ST28-infected MDDC compared to H37Rv- or ST29-infected cell results. However, in spite of the presence of IL-10, supernatants from ST28-infected DC induced IFN-{gamma} production by T cells similarly to those from H37Rv-infected DC culture. On the other hand, IL-10 impaired CXCL10 production in sigE mutant-infected DC and, indeed, its neutralization restored CXCL10 secretion. In line with these results, supernatants from ST28-infected cells showed a decreased capability to recruit CXCR3+ CD4+ T cells compared to those obtained from H37Rv-infected DC culture. Thus, our findings suggest that the sigE mutant-induced secretion of IL-10 inhibits CXCL10 expression and, in turn, the recruitment of activated-effector cells involved in the formation of granulomas.

* Corresponding author. Mailing address: Department of Infectious, Parasitic, and Immuno-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy. Phone: 390649903638. Fax: 390649387112. E-mail: e.coccia{at}iss.it.

Editor: J. L. Flynn

Infection and Immunity, June 2006, p. 3296-3304, Vol. 74, No. 6
0019-9567/06/$08.00+0     doi:10.1128/IAI.01687-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Giacomini, E., Remoli, M. E., Gafa, V., Pardini, M., Fattorini, L., Coccia, E. M. (2009). IFN-{beta} improves BCG immunogenicity by acting on DC maturation. J. Leukoc. Biol. 85: 462-468 [Abstract] [Full Text]  
  • Dona, V., Rodrigue, S., Dainese, E., Palu, G., Gaudreau, L., Manganelli, R., Provvedi, R. (2008). Evidence of Complex Transcriptional, Translational, and Posttranslational Regulation of the Extracytoplasmic Function Sigma Factor {sigma}E in Mycobacterium tuberculosis. J. Bacteriol. 190: 5963-5971 [Abstract] [Full Text]  


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