This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Giacomini, E. Articles by Coccia, E. M. Search for Related Content PubMed PubMed Citation Articles by Giacomini, E. Articles by Coccia, E. M.

 Previous Article  |  Next Article 

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

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 ^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- 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.

Editor: J. L. Flynn

This article has been cited by other articles:

• 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]