Direct anti-inflammatory effect of a bacterial virulence factor: IL-10-dependent suppression of IL-12 production by filamentous hemagglutinin from Bordetella pertussis

IL-12 plays a critical role in protective immunity against intracellular pa thogens by promoting the development of Th1 cells. Here we demonstrate that filamentous hemagglutinin (FHA), a virulence factor of Bordetella pertussi s, is capable of suppressing IL-12 production by macrophages. FHA inhibited IL-12 secretion by a macrophage cell line or ex vivo alveolar macrophages in response to Escherichia coil or B. pertussis lipopolysaccharide (LPS) an d IFN-gamma. Antibodies to FHA or denaturation of FHA abrogated the inhibit ory effect. Injection of mice with FHA suppressed IL-12 and IFN-gamma level s in the serum in response to i.v. injection of LPS in a model of septic sh ock. The suppressive effect of FHA was specific for IL-12, since the produc tion of TNF-alpha, IL-6 and IL-10 was not suppressed, and production of IL- 6 and IL-10 was up-regulated. Antibody blocking studies revealed that the i nhibitory effect of FHA on IL-12 production was dependent on IL-10. Since F HA is secreted at high levels and local T cell responses are suppressed dur ing B. pertussis infection, the findings suggest that FHA may be a critical virulence factor in facilitating pathogen persistence in the respiratory t ract by suppressing or delaying the development of cell-mediated immunity.