Brucella abortus lipoproteins inhibit MHC class II expression and antigen processing of human monocyte/macrophages through IL-6 secretion via TLR2.

BARRIONUEVO, PAULA; CASSATARO, JULIANA; DELPINO, MARÍA VICTORIA; ZWERDLING, ASTRID; PASQUEVICH, KARINA; GARCÍA SAMARTINO, CLARA; WALLACH, JORGE; FOSSATI, ALBERTO; GIAMBARTOLOMEI, GUILLERMO

Río de Janeiro, Brasil.

Congreso; 13th International Congress of Immunology; 2007

Asociación latinoamericana de Inmunología (ALAI)

The strategies that allow Brucella abortus to survive inside macrophages for prolonged periods avoiding the immunological surveillance of MHC class II (MHC-II)-restricted IFN-g-producing CD4+ T lymphocytes are poorly understood. We report herein that infection of THP-1 cells with B. abortus inhibited expression of MHC-II molecules and antigen processing. Heat-killed B. abortus (HKBA) also induced both phenomena, indicating independency of bacterial viability and involvement of a structural component of the bacterium. Accordingly, outer membrane protein 19 (L-Omp19), a prototypical B. abortus lipoprotein, inhibited both MHC-II expression and antigen processing to the same extent of HKBA in THP-1 cells. Moreover, a synthetic lipohexapeptide that mimics the structure of the protein lipid moiety also inhibited MHC-II expression, indicating that any Brucella lipoprotein could down-modulate MHC-II expression and antigen processing. Inhibition of MHC-II expression and antigen processing by either HKBA or L-Omp19 depends on TLR2 and is mediated by IL-6. HKBA or L-Omp19 also inhibited MHC-II expression and antigen processing of human monocytes. In addition, exposure to the synthetic lipohexapeptide inhibited antigen-specific T cell proliferation and IFN-g production of PBMC from Brucella-infected patients. Together, these results entail a mechanism whereby B. abortus may prevent recognition by T cells to evade host immunity, establishing a chronic infection.