Brucella lipoproteins mimic dendritic cell maturation induced by Brucella abortus

• Published in: Microbes and infection 2008-10, Vol.10 (12), p.1346-1354
• Main Authors: Zwerdling, Astrid, Delpino, M. Victoria, Barrionuevo, Paula, Cassataro, Juliana, Pasquevich, Karina A., García Samartino, Clara, Fossati, Carlos A., Giambartolomei, Guillermo H.
• Format: Article
• Language: English
• Subjects: Antigens, Bacterial - immunology; Bacterial diseases; Bacterial Outer Membrane Proteins - immunology; Bacteriology; Biological and medical sciences; Brucella; Brucella abortus; Brucella abortus - pathogenicity; Brucellosis; Cell Differentiation; Cytokines - metabolism; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - microbiology; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Human bacterial diseases; Humans; Infectious diseases; Lipoproteins; Lipoproteins - immunology; Medical sciences; Microbiology; Miscellaneous; Receptors, Cell Surface - metabolism
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2008.07.035

Infection with Brucella abortus induces a pro-inflammatory response that drives T cell responses toward a Th1 profile. The mechanism by which this bacterium triggers this response is unknown. Dendritic cells (DC) are crucial mediators at the host-pathogen interface and are potent Th1-inducing antigen-presenting cells. Thus, we examined the mechanism whereby B. abortus stimulate human DC maturation. B. abortus-infected DC increased the expression of CD86, CD80, CCR7, CD83, MHCII, MHCI and CD40 and induced the production of TNF-α, IL-6, IL-10 and IL-12. Both phenomena were not dependent on bacterial viability since they were also induced by heat-killed B. abortus (HKBA). B. abortus LPS was unable to induce markers up-regulation or cytokine production. We next investigated the capacity of the outer membrane protein 19 (Omp19) as a B. abortus lipoprotein model to induce DC maturation. Lipidated Omp19 (L-Omp19), but not its unlipidated form, increased the expression of cell surface markers and the secretion of cytokines. L-Omp19-matured DC also have decreased endocytic activity and displayed enhanced T cell stimulatory activity in a MLR. Pre-incubation of DC with anti-TLR2 mAb blocked L-Omp19-mediated cytokine production. These results demonstrate that B. abortus lipoproteins can stimulate DC maturation providing a mechanism by which these bacteria generate a Th1-type immune response.