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Infection and Immunity, October 2007, p. 4980-4989, Vol. 75, No. 10
0019-9567/07/$08.00+0     doi:10.1128/IAI.00637-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Brucella suis Prevents Human Dendritic Cell Maturation and Antigen Presentation through Regulation of Tumor Necrosis Factor Alpha Secretion{triangledown}

Elisabeth Billard, Jacques Dornand, and Antoine Gross*

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

Received 7 May 2007/ Returned for modification 21 June 2007/ Accepted 2 July 2007

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 the initial exposure. The 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 are a preferential niche for the development of the bacteria. Here, we report that in contrast to several intracellular bacteria, Brucella prevented the infected DCs from engaging in their maturation process and impaired their capacities to present antigen to naïve T cells and to secrete interleukin-12. Moreover, Brucella-infected DCs failed to release tumor necrosis factor alpha (TNF-{alpha}), a defect involving the bacterial protein Omp25. Exogenous TNF-{alpha} addition to Brucella-infected DCs restored cell maturation and allowed them to present antigens. Two avirulent mutants of B. suis, B. suis bvrR and B. suis omp25 mutants, which do not express the Omp25 protein, triggered TNF-{alpha} production upon DC invasion. Cells infected with these mutants subsequently matured and acquired the ability to present antigens, two properties which were dramatically impaired by addition of anti-TNF-{alpha} antibodies. In light of these data, we propose a model in which virulent Brucella alters the maturation and functions of DCs through Omp25-dependent control of TNF-{alpha} production. This model defines a specific evasion strategy of the bacteria by which they can escape the immune response to chronically infect their host.

* Corresponding author. Mailing address: CPBS UMR CNRS 5236 UM1 UM2, Université Montpellier II, cc100, Place E. Bataillon, 34095 Montpellier, France. Phone: (33) 4 67 14 32 09. Fax: (33) 4 67 14 33 38. E-mail: gross{at}univ-montp2.fr

{triangledown} Published ahead of print on 16 July 2007.

Editor: D. L. Burns

Infection and Immunity, October 2007, p. 4980-4989, Vol. 75, No. 10
0019-9567/07/$08.00+0     doi:10.1128/IAI.00637-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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]  


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