IL-10 induction by Bordetella parapertussis limits a protective IFN-gamma response

• Published in: The Journal of immunology (1950) 2010-02, Vol.184 (3), p.1392-1400
• Main Authors: Wolfe, Daniel N, Karanikas, Alexia T, Hester, Sara E, Kennett, Mary J, Harvill, Eric T
• Format: Article
• Language: English
• Subjects: Animals; Bordetella Infections - immunology; Bordetella Infections - microbiology; Bordetella Infections - pathology; Bordetella parapertussis - growth & development; Bordetella parapertussis - immunology; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; Bronchoalveolar Lavage Fluid - microbiology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - microbiology; CD4-Positive T-Lymphocytes - pathology; Cell Line, Transformed; Cell Migration Inhibition - genetics; Cell Migration Inhibition - immunology; Inflammation Mediators - metabolism; Inflammation Mediators - physiology; Interferon-gamma - antagonists & inhibitors; Interferon-gamma - biosynthesis; Interferon-gamma - deficiency; Interferon-gamma - physiology; Interleukin-10 - biosynthesis; Interleukin-10 - deficiency; Interleukin-10 - genetics; Interleukin-10 - physiology; Lung - immunology; Lung - microbiology; Lung - pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0803045

Bordetella parapertussis causes the prolonged coughing illness known as pertussis or whooping cough, persisting for weeks within the respiratory tracts of infected hosts but inducing a very poor T cell response relative to that induced by Bordetella pertussis, the more common cause of pertussis. In this study, we examine the contributions of cytokines involved in the clearance of B. parapertussis and immunomodulation that delays effective clearance. The slow elimination of this pathogen from the respiratory tracts of mice coincides with the gradual accumulation of CD4(+) T cells in the lungs and B. parapertussis-responsive IFN-gamma-producing cells in the spleen. IFN-gamma-deficient mice were defective in the accumulation of leukocytes in lungs and in clearance of B. parapertussis from the lungs. In vitro B. parapertussis-stimulated macrophages produced IL-10, which inhibited the generation of the IFN-gamma response that is required for protection in vivo. As compared with wild-type mice, IL-10-deficient mice produced significantly higher levels of IFN-gamma, had higher numbers of leukocytes accumulated in the lungs, and cleared B. parapertussis more rapidly. Together, these data indicate that B. parapertussis induces the production of IL-10, which facilitates its persistence within infected hosts by limiting a protective IFN-gamma response.