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Impaired maturation and function of dendritic cells by mycobacteria through IL-1beta.

Abstract

Dendritic cells (DC) are pivotal for initiation and regulation of innate and adaptive immune responses evoked by vaccination and natural infection. After infection, mycobacterial pathogens first encounter monocytes, which produce pro-inflammatory cytokines, including IL-1beta, TNF-alpha and IL-6. The role of these cytokines in DC maturation remains incompletely understood. Here, we show that maturation of DC from monocytes was impaired by pretreatment of monocytes with low doses of IL-1beta. Under these conditions, Mycobacterium leprae-infected DC failed to stimulate antigen-specific T cell responses. Expression of CD86 and CD83 and production of IL-12 in response to lipopolysaccharide and peptidoglycan were diminished. In contrast, these DC functions were not impaired by pretreatment with TNF-alpha, IL-6 or IL-10. When monocytes were infected with M. bovis Bacillus Calmette-Guérin, and subsequently differentiated to DC, the activity of these DC was suppressed as well. Thus, IL-1beta acts at early stages of differentiation of DC and impairs biological functions of DC at later stages. Therefore, production of IL-1beta by mycobacteria-infected antigen-presenting cells counteracts effective stimulation of innate and adaptive immune responses.

More information

Type
Journal Article
Author
Makino M
Maeda Y
Mukai T
Kaufmann SH E
Year of Publication
2006
Journal
European journal of immunology
Volume
36
Issue
6
Number of Pages
1443-52
Date Published
2006 Jun
Language
eng
ISSN Number
0014-2980
DOI
10.1002/eji.200535727
Alternate Journal
Eur. J. Immunol.
Publication Language
eng