A Polymeric Bacterial Protein Activates Dendritic Cells Via TLR4

BERGUER, P. M., MUNDIÑANO, J., PIAZZON, I. AND GOLDBAUM, F. A.

JOURNAL OF IMMUNOLOGY

Año: 2006 vol. 176 p. 2366 - 2372

0022-1767

The enzyme lumazine synthase from Brucella spp. (BLS) is a highly immunogenic protein that folds as a stable dimer of pentamers.It is possible to insert foreign peptides and proteins at the 10 N terminus of BLS without disrupting its general folding, and thesechimeras are very efficient to elicit systemic and oral immunity without adjuvants. In this study, we show that BLS stimulates bonemarrow dendritic cells from mice in vitro to up-regulate the levels of costimulatory molecules (CD40, CD80, and CD86) and majorhistocompatibility class II Ag. Furthermore, the mRNA levels of several chemokines are increased, and proinflammatory cytokinesecretion is induced upon exposure to BLS. In vivo, BLS increases the number of dendritic cells and their expression of CD62Lin the draining lymph node. All of the observed effects are dependent on TLR4, and clearly independent