Brucella abortus inhibits major histocompatibility complex class II expression and antigen processing through IL-6 secretion via TLR-2

BARRIONUEVO P., CASSATARO J., DELPINO M. V., ZWERDLING A., PASQUEVICH K. A., GARCÍA SAMARTINO C., WALLACH J. C., FOSSATI C. A., GIAMBARTOLOMEI G. H.

INFECTION AND IMMUNITY

American Society of Microbiology

Año: 2008 vol. 76 p. 250 - 262

0019-9567

The strategies that allow Brucella abortus to survive inside macrophages for prolonged periods avoiding the immunological surveillance of major histocompatibility complex class II (MHC-II)-restricted gamma interferon (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 (Ag) 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 (Omp19), a prototypical B. abortus lipoprotein, inhibited both MHC-II expression and Ag processing to the same extent of HKBA. 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 Ag processing. Inhibition of MHC-II expression and Ag processing by either HKBA or L-Omp19 depends on toll-like receptor 2 and is mediated by interleukin-6. HKBA or L-Omp19 also inhibited MHC-II expression and Ag processing of human monocytes. In addition, exposure to the synthetic lipohexapeptide inhibited Ag-specific T cell proliferation and IFN-g production of peripheral blood mononuclear cells 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.