Brucella abortus inhibits IFN-ã-induced FcãRI expression and FcãRI-restricted phagocytosis via toll-like receptor 2 on human monocytes/macrophages

BARRIONUEVO, P; DELPINO MV; VELÁSQUEZ LN; SAMARTINO CG; CORIA LM; IBAÑEZ AE; RODRÍGUEZ ME; CASSATARO J; GIAMBARTOLOMEI GH

MICROBES AND INFECTION

ELSEVIER SCIENCE BV

Año: 2010

1286-4579

The strategies that allow B. abortus to persist for years inside macrophages subverting 3 host immune responses are not completely understood. Immunity against this bacterium relies on the capacity of IFN-g 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 (FcgRI, CD64) and FcgRI-restricted phagocytosis regulated by IFN-g 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 FcgRI-restricted phagocytosis regulated by IFN-g. 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 FcgRI-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-g and to subvert host immunonological responses. [Epub ahead of print]