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© The Rockefeller University Press, 0022-1007/1997/12/1843/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 11, December 1, 1997 1843-1851

Articles

Atypical Disease after Bordetella pertussis Respiratory Infection of Mice with Targeted Disruptions of Interferon-{gamma} Receptor or Immunoglobulin µ Chain Genes

Bernard P. Mahon*, Brian J. Sheahan{ddagger}, Fiona Griffin*, Geraldine Murphy*, and Kingston H.G. Mills*

From the * Infection and Immunity Group, Department of Biology, National University of Ireland, Maynooth, County Kildare, Ireland; and the {ddagger} Department of Veterinary Pathology, University College Dublin, Dublin, Ireland

Using a murine respiratory challenge model we have previously demonstrated a role for Th1 cells in natural immunity against Bordetella pertussis, but could not rule out a role for antibody. Here we have demonstrated that B. pertussis respiratory infection of mice with targeted disruptions of the genes for the IFN-{gamma} receptor resulted in an atypical disseminated disease which was lethal in a proportion of animals, and was characterized by pyogranulomatous inflammation and postnecrotic scarring in the livers, mesenteric lymph nodes and kidneys. Viable virulent bacteria were detected in the blood and livers of diseased animals. An examination of the course of infection in the lung of IFN-{gamma} receptor–deficient, IL-4–deficient and wild-type mice demonstrated that lack of functional IFN-{gamma} or IL-4, cytokines that are considered to play major roles in regulating the development of Th1 and Th2 cells, respectively, did not affect the kinetics of bacterial elimination from the lung. In contrast, B cell–deficient mice developed a persistent infection and failed to clear the bacteria after aerosol inoculation. These findings demonstrate an absolute requirement for B cells or their products in the resolution of a primary infection with B. pertussis, but also define a critical role for IFN-{gamma} in containing bacteria to the mucosal site of infection.

Address correspondence to Dr. Kingston Mills, Infection and Immunity Group, National University of Ireland Maynooth, Co. Kildare, Ireland. Tel.: (+353) 1-708-3838; Fax: (+353) 1-708-3845; E-mail: kmills{at}may.ie

1 Abbreviations used in this paper: FHA, and filamentous hemagglutinin; IFN-{gamma}R, IFN-{gamma} receptor; PT, pertussis toxin.


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