Brucella lipoproteins mimic dendritic cell maturation induced by Brucella abortus.
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-alpha, 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.
Zwerdling
Astrid
A
Instituto de Estudios de la Inmunidad Humoral (CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires (U.B.A.), Buenos Aires, Argentina.
Delpino
M Victoria
MV
Barrionuevo
Paula
P
Cassataro
Juliana
J
Pasquevich
Karina A
KA
García Samartino
Clara
C
Fossati
Carlos A
CA
Giambartolomei
Guillermo H
GH