CHLAMYDIAL INFECTION IN INDUCIBLE NITRIC-OXIDE SYNTHASE KNOCKOUT MICE

Type 1 CD4(+)-T-cell-mediated immunity is crucial for the resolution o f chlamydial infection of the murine female genital tract. Previous st udies demonstrating a correlation between CD4(+)-T-cell-mediated inhib ition of chlamydial growth and gamma interferon (IFN-gamma)-mediated i nduction of nitric oxide synthase suggested a potential role for the n itric oxide (NO) effector pathway in the clearance of Chlamydia from g enital epithelial cells by the immune system. To clarify the role of t his pathway, the growth levels of Chlamydia trachomatis organisms in n ormal (iNOS(+/+)) mice and in genetically engineered mice lacking the inducible nitric oxide synthase (iNOS) gene (iNOS(-/-)mice) were compa red. There was no significant difference in the course of genital chla mydial infections in iNOS(+/+) and iNOS(-/-)mice as determined by reco very of Chlamydia organisms shed from genital epithelial cells. Dissem ination of Chlamydia to the spleen and lungs occurred to a greater ext ent in iNOS(-/-)than in iNOS(+/+) mice, which correlated with a margin al increase in the susceptibility of macrophages from iNOS(-/-)mice to chlamydial infection in vitro. However, infections were rapidly clear ed from all affected tissues, with no clinical signs of disease. The f inding of minimal dissemination in iNOS(-/-)mice suggested that activa tion of the iNOS effector pathway was not the primary target of IFN-ga mma during CD4(+)-T-cell-mediated control of chlamydial growth in macr ophages because previous reports demonstrated extensive and often fata l dissemination of Chlamydia in mice lacking IFN-gamma. In summary, th ese results indicate that the iNOS effector pathway is not required fo r elimination of Chlamydia from epithelial cells lining the female gen ital tract of mice although it may contribute to the control of dissem ination of C. trachomatis by infected macrophages.