INVESTIGADORES
GIAMBARTOLOMEI Guillermo Hernan
congresos y reuniones científicas
Título:
Brucella abortus lipoproteins inhibit MHC class II expression and antigen processing of human monocyte/macrophages through IL-6 secretion via TLR2.
Autor/es:
P. BARRIONUEVO, J. CASSATARO, M. V. DELPINO, A. ZWERDLING, K. A. PASQUEVICH, C. GARCÍA SAMARTINO, JORGE C. WALLACH, CARLOS A. FOSSATI, G. H. GIAMBARTOLOMEI.
Lugar:
Río de Janeiro
Reunión:
Congreso; 13th Congress of Immunology; 2007
Institución organizadora:
IUIS
Resumen:
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.
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