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Clinical and Developmental Immunology
Volume 2011, Article ID 841346, 8 pages
http://dx.doi.org/10.1155/2011/841346
Research Article

Expression of Proinflammatory and Regulatory Cytokines via NF-κB and MAPK-Dependent and IFN Regulatory Factor-3-Independent Mechanisms in Human Primary Monocytes Infected by Mycobacterium tuberculosis

1Dipartimento di Malattie Infettive, Parassitarie ed Immmuno-mediate, Istituto Superiore di Sanità, I-00161, Rome, Italy
2EA4303 “Inflammation et Immunité de l'épithélium Respiratoire”, IFR53, UFR de Pharmacie, Université de Reims Champagne-Ardenne, 51096 Reims, France

Received 14 October 2010; Accepted 26 November 2010

Academic Editor: James Triccas

Copyright © 2011 Elena Giacomini et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Knowledge of the molecular events regulating the innate response to Mycobacterium tuberculosis (Mtb) is critical for understanding immunological pathogenesis and protection from tuberculosis. To this aim, the regulation and the expression of regulatory and proinflammatory cytokines were investigated in human primary monocytes upon Mtb infection. We found that Mtb-infected monocytes preferentially express a proinflammatory cytokine profile, including IL-6, TNF-α, and IL-1β. Conversely, among the regulatory cytokines, Mtb elicited IL-10 and IL-23 release while no expression of IL-12p70, IL-27, and IFN-β was observed. The analysis of the signalling pathways leading to this selective cytokine expression showed that in monocytes Mtb activates MAPK and NF-κB but is unable to stimulate IRF-3 phosphorylation, a transcription factor required for IL-12p35 and IFN-β gene expression. Thus, by inducing a specific cytokine profile, Mtb can influence the immunoregulatory properties of monocytes, which represent important target of novel vaccinal strategies against Mtb infection.