Brucella abortus inhibits IFN-γ-induced FcγRI expression and FcγRI-restricted phagocytosis via toll-like receptor 2 on human monocytes/macrophages.
The strategies that allow Brucella abortus to persist for years inside macrophages subverting host immune responses are not completely understood. Immunity against this bacterium relies on the capacity of IFN-γ to activate macrophages, endowing them with the ability to destroy intracellular bacteria. We report here that infection with B. abortus down-modulates the expression of the type I receptor for the Fc portion of IgG (FcγRI, CD64) and FcγRI-restricted phagocytosis regulated by IFN-γ in human monocytes/macrophages. Both phenomena were not dependent on bacterial viability, since they were also induced by heat-killed B. abortus (HKBA), suggesting that they were elicited by a structural bacterial component. Accordingly, a prototypical B. abortus lipoprotein (L-Omp19), but not its unlipidated form, inhibited both CD64 expression and FcγRI-restricted phagocytosis regulated by IFN-γ. Moreover, a synthetic lipohexapeptide that mimics the structure of the protein lipid moiety also inhibited CD64 expression, indicating that any Brucella lipoprotein could down-modulate CD64 expression and FcγRI-restricted phagocytosis. Pre-incubation of monocytes/macrophages with anti-TLR2 mAb blocked the inhibition of the CD64 expression mediated by HKBA and L-Omp19. These results, together with our previous observations establish that B. abortus utilizes its lipoproteins to inhibit the monocytes/macrophages activation mediated by IFN-γ and to subvert host immunonological responses.
Instituto de Estudios de la Inmunidad Humoral (CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina.
Paula
P
Barrionuevo
M Victoria
MV
Delpino
Lis N
LN
Velásquez
Clara
C
García Samartino
Lorena M
LM
Coria
Andrés E
AE
Ibañez
María Eugenia
ME
Rodríguez
Juliana
J
Cassataro
Guillermo H
GH
Giambartolomei
D000942:Antigens, Bacterial / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D002003:Brucella abortus / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D010587:Phagocytosis / Q000502:physiology; D017452:Receptors, IgG / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D018709:Statistics, Nonparametric; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; C489017:FCGR1A protein, human; D008074:Lipoproteins; C097319:OMP19 protein, Brucella abortus; D017452:Receptors, IgG; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D007371:Interferon-gamma