ROLE OF GAMMA-INTERFERON IN NATURAL CLEARANCE OF BORDETELLA-PERTUSSISINFECTION

Using a mouse model of Bordetella pertussis infection, we have analyze d the role of gamma interferon (IFN-gamma) in bacterial clearance from the respiratory tract. Adult BALB/c mice began to clear a respiratory infection within 3 weeks postinfection, with complete resolution of i nfection 6 to 8 weeks postinfection. In contrast, neither adult SCID m ice (which lack mature B and T lymphocytes) nor adult nude mice (which lack mature T lymphocytes) controlled B. pertussis infection, and bot h strains died within 3 to 5 weeks postinfection. Short-term T-cell Li nes generated from the draining lymph nodes of the lungs of infected B ALB/c mice were found to be CD4(+) and produced IFN-gamma but no detec table interleukin-4. Analyses of IFN-gamma mRNA induction in the lungs of mice following B. pertussis infection showed that in both BALB/c a nd C57/BL/6 mice, IFN-gamma mRNA levels increased sharply by 1 week po stinfection and then subsequently declined. Further exploration of a p otential role for IFN-gamma demonstrated that infection of adult BALB/ c mice depleted of IFN-gamma in vivo with anti-IFN-gamma monoclonal an tibodies resulted in greater numbers of bacteria recovered from the lu ngs than in infected, control BALB/c mice, although IFN-gamma-depleted mice could subsequently clear the infection, Infection of mice which have a disrupted IFN-gamma gene resulted in bacterial clearance with a time course similar to those seen with IFN-gamma-depleted mice. These results indicate that IFN-gamma plays a role in controlling B. pertus sis infection.