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 pathogens by promoting the development of Th1 cells. Here we demonstrate that filamentous hemagglutinin (FHA), a virulence factor of Bordetella pertussis, 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 coli or B. pertussis lipopolysaccharide (LPS) and IFN-gamma. Antibodies to FHA or denaturation of FHA abrogated the inhibitory effect. Injection of mice with FHA suppressed IL-12 and IFN-gamma levels in the serum in response to i. v. injection of LPS in a model of septic shock. The suppressive effect of FHA was specific for IL-12, since the production 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 inhibitory effect of FHA on IL-12 production was dependent on IL-10. Since FHA is secreted at high levels and local T cell responses are suppressed during B. pertussis infection, the findings suggest that FHA may be a critical virulence factor in facilitating pathogen persistence in the respiratory tract by suppressing or delaying the development of cell-mediated immunity.
McGuirk
P
P
Infection and Immunity Group, National University of Ireland, Maynooth, Ireland.
Mills
K H
KH
D000818:Animals; D001886:Bordetella pertussis / Q000276:immunology*; D006388:Hemagglutinins / Q000276:immunology* / Q000494:pharmacology; D007109:Immunity; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014917:Whooping Cough / Q000276:immunology / Q000382:microbiology
D006388:Hemagglutinins; D016753:Interleukin-10; D018664:Interleukin-12