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

P. BARRIONUEVO; M. V. DELPINO; L. N. VELASQUEZ; C GARCÍA SAMARTINO; L. M. CORIA; A. E. IBANEZ; M.E. RDRIGUEZ; J. CASSATARO; G. H. GIAMBARTOLOMEI

MICROBES AND INFECTION

ELSEVIER SCIENCE BV

Año: 2010

1286-4579

The strategies that allow B. abortus to persist for years inside macrophages subverting hostimmune responses are not completely understood. Immunity against this bacterium relies on thecapacity of IFN-gamma to activate macrophages, endowing them with the ability to destroyintracellular bacteria. We report here that infection with B. abortus down-modulates the expression ofthe type I receptor for the Fc portion of IgG (FcgammaRI, CD64) and FcgammaRI-restrictedphagocytosis regulated by IFN-gamma 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 by a structural bacterial component. Accordingly, a prototypical B.abortus lipoprotein (L-Omp19), but not its unlipidated form, inhibited both CD64 expression and-restricted phagocytosis regulated by IFN-gamma. Moreover, a synthetic lipohexapeptide thatmimics the structure of the protein lipid moiety also inhibited CD64 expression, indicating that anyBrucella lipoprotein could down-modulate CD64 expression and FcgammaRI-restricted phagocytosis.Pre-incubation of monocytes/macrophages with anti-TLR2 mAb blocked the inhibition of the CD64expression mediated by HKBA and L-Omp19. These results, together with our previous observationsestablish that B. abortus utilizes its lipoproteins to inhibit the monocytes/macrophages activationmediated by IFN-gamma and to subvert host immunonological responses.