Brucella abortus inhibits IFN-g-induced Fc;RI expression and FcγRI-restricted phagocytosis via Toll-Like Receptor 2 on human monocytes/macrophages

BARRIONUEVO PAULA; DELPINO VICTORIA; VELASKEZ, LIS; GARCÍA SAMARTINO CLARA; CORIA LM; IBAÑEZ AE; RODRIGUEZ ME; CASSATARO JULIANA; GIAMBARTOLOMEI GH

MICROBES AND INFECTION

ELSEVIER SCIENCE BV

Año: 2011 p. 239 - 250

1286-4579

The strategies that allow Brucella abortus to persist for years inside macrophages subverting host immune responses are not completelyunderstood. Immunity against this bacterium relies on the capacity of IFN-g to activate macrophages, endowing them with the ability to destroyintracellular bacteria. We report here that infection with B. abortus down-modulates the expression of the type I receptor for the Fc portion ofIgG (FcgRI, CD64) and FcgRI-restricted phagocytosis regulated by IFN-g in human monocytes/macrophages. Both phenomena were notdependent on bacterial viability, since they were also induced by heat-killed B. abortus (HKBA), suggesting that they were elicited bya structural bacterial component. Accordingly, a prototypical B. abortus lipoprotein (L-Omp19), but not its unlipidated form, inhibited bothCD64 expression and FcgRI-restricted phagocytosis regulated by IFN-g. Moreover, a synthetic lipohexapeptide that mimics the structure of theprotein lipid moiety also inhibited CD64 expression, indicating that any Brucella lipoprotein could down-modulate CD64 expression and FcgRIrestrictedphagocytosis. Pre-incubation of monocytes/macrophages with anti-TLR2 mAb blocked the inhibition of the CD64 expressionmediated by HKBA and L-Omp19. These results, together with our previous observations establish that B. abortus utilizes its lipoproteins toinhibit the monocytes/macrophages activation mediated by IFN-g and to subvert host immunonological responses.