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Direct anti‐inflammatory effect of a bacterial virulence factor: IL‐10‐dependent suppression of IL‐12 production by filamentous hemagglutinin from Bordetella pertussis
Author(s) -
McGuirk Peter,
Mills Kingston H. G.
Publication year - 2000
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/1521-4141(200002)30:2<415::aid-immu415>3.0.co;2-x
Subject(s) - filamentous haemagglutinin adhesin , biology , microbiology and biotechnology , bordetella pertussis , hemagglutinin (influenza) , lipopolysaccharide , antibody opsonization , virulence factor , virulence , pertussis toxin , cytokine , antibody , immunology , phagocytosis , bacteria , signal transduction , g protein , gene , opsonin , genetics , biochemistry
Abstract 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‐γ. Antibodies to FHA or denaturation of FHA abrogated the inhibitory effect. Injection of mice with FHA suppressed IL‐12 and IFN‐γ 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‐α, 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.