- Brucella spp. lumazine synthase (BLS) activates dendritic cells via Toll-Like receptor 4 (TLR4).

BERGUER P, MUNDIÑANO J, PIAZZON I, GOLDBAUM F

Córdoba, Argentina

Congreso; VII Congreso Latinoamericano de Inmunología; 2005

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-fareast-language:EN-US;} @page Section1 {size:612.0pt 792.0pt; margin:56.75pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> BLS is a highly immunogenic protein. We have shown that it stimulates bone marrow dendritic cells (BMDCs) to upregulate the levels of costimulatory molecules and MHCII antigen and to secrete proinflammatory cytokines, being these effects dependent on TLR4 and independent of LPS. Objective: To further study the consequences of TLR4 signaling in BLS stimulation. We analyzed chemokine mRNA levels in BLS-stimulated BMDCs by RNAse Protection Assays. After 18h of BLS exposure (10mM), BALB/c BMDCs significantly increased the levels of MIP-1a, MIP-1b, MIP-2, MCP-1 and RANTES (1.2-3.7 fold). None of these mRNAs were induced in BMDCs from TLR4-defective C.C3H-Tlr4lps-d mice. We then injected 10mg of BLS into BALB/c and C.C3H-Tlr4lps-d mice footpads and 2 days later the popliteal lymph nodes were subjected to FACS. In BALB/c mice, BLS significantly increased the absolute number of CD11c+ cells (33.8±9.8 vs 4.7±1.1 x104, p<0.01) and the percentage and absolute number of dendritic cells (DCs) expressing high levels of CD62L in the draining lymph node. BLS did not lead to those increases in C.C3H-Tlr4lps-d mice. BLS inoculation induced a TLR4-dependent recruitment of DCs to the draining lymph node. This effect is probably mediated by increases in the expression of chemokines known to attract immature DCs into the vicinity of pathogens.