Brucella abortus inhibits major histocompatibility complex class II expression and antigen processing through interleukin-6 secretion via Toll-like receptor 2.
The strategies that allow Brucella abortus to survive inside macrophages for prolonged periods and to avoid the immunological surveillance of major histocompatibility complex class II (MHC-II)-restricted gamma interferon (IFN-gamma)-producing CD4+ T lymphocytes are poorly understood. We report here 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 these phenomena, indicating the independence 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 as 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 lipidated Omp19 (L-Omp19) depended on Toll-like receptor 2 and was 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-gamma production of peripheral blood mononuclear cells from Brucella-infected patients. Together, these results indicate that there is a mechanism by which B. abortus may prevent recognition by T cells to evade host immunity and establish a chronic infection.
Barrionuevo
Paula
P
Instituto de Estudios de la Inmunidad Humoral (IDEHU), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, 1113 Buenos Aires, Argentina.
Cassataro
Juliana
J
Delpino
M Victoria
MV
Zwerdling
Astrid
A
Pasquevich
Karina A
KA
García Samartino
Clara
C
Wallach
Jorge C
JC
Fossati
Carlos A
CA
Giambartolomei
Guillermo H
GH
D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D002003:Brucella abortus / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured; D015536:Down-Regulation; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma; D015850:Interleukin-6 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000382:microbiology; D008074:Lipoproteins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D015850:Interleukin-6; D008074:Lipoproteins; C097319:OMP19 protein, Brucella abortus; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D007371:Interferon-gamma