This Article Full Text (PDF) Other Versions of this Article: IAI.00637-07v1 75/10/4980    most recent 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 Billard, E. Articles by Gross, A. Search for Related Content PubMed PubMed Citation Articles by Billard, E. Articles by Gross, A.

 Previous Article  |  Next Article 

Infect. Immun. doi:10.1128/IAI.00637-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Brucella suis prevent human dendritic cell maturation and antigen presentation through the regulation of TNF- secretion

INSERM U431, CPBS UMR CNRS 5236 UM1 UM2, F-34095 Montpellier, France

^* To whom correspondence should be addressed. Email: gross{at}univ-montp2.fr.

	Abstract

Brucella is a facultative intracellular pathogen and the etiological agent of brucellosis. In some cases, human brucellosis results in a persistent infection that may reactivate years after initial exposure. Mechanisms by which the parasite evades clearance by the immune response to chronically infect its host are unknown. We recently demonstrated that dendritic cells (DCs), which are critical components of adaptive immunity, are highly susceptible to Brucella infection and constitute a preferential niche for the development of the bacteria. Here, we report that contrary to several intracellular bacteria, Brucella prevented the infected DCs from engaging their maturation process and impaired their capacity to present antigen to naive T cells and to secrete IL-12. Moreover, Brucella infected DCs failed to release TNF-, a defect involving the bacterial protein Omp25. Exogenous TNF- addition to Brucella-infected DCs restored cell maturation and allowed them to present antigens. Two avirulent mutants of B.suis, bvrR B.suis and omp25 B.suis, which do not express the Omp25 protein, triggered TNF- production upon DC invasion. Cells infected with these mutants subsequently matured and acquired the function to present antigens, two properties which were dramatically impaired by addition of anti TNF- antibodies. In light of these data, we propose a model whereby virulent Brucella alter the maturation and functions of DCs through an Omp25-dependent control of TNF- production. This model defines a specific evasion strategy of the bacteria by which they can escape the immune response to chronically infect their host.

This article has been cited by other articles:

• Billard, E., Dornand, J., Gross, A. (2007). Interaction of Brucella suis and Brucella abortus Rough Strains with Human Dendritic Cells. Infect. Immun. 75: 5916-5923 [Abstract] [Full Text]