Genital tract infection with Chlamydia trachomatis fails to induce protective immunity in gamma interferon receptor-deficient mice despite a strong local immunoglobulin A response.
CD4+ T cells have been found to play a critical role in immune protection against Chlamydia trachomatis infection. Since both humoral and cell-mediated antichlamydial immunity have been implicated in host protection, the crucial effector functions provided by the CD4+ T cells may rely on Th1 or Th2 functions or both. In the present study, we evaluated the development of natural immunity following vaginal infection with C. trachomatis serovar D in female gamma interferon receptor-deficient (IFN-gammaR-/-) mice with a disrupted Th1 effector system. We found that in comparison with wild-type mice, the IFN-gammaR-/- mice exhibited a severe ascending primary infection of prolonged duration which stimulated almost 10-fold-stronger specific local immunoglobulin A (IgA) and IgG responses in the genital tract. Following resolution of the primary infection and despite the augmented antibody responses to chlamydiae, the IFN-gammaR-/- mice were completely unprotected against reinfection, suggesting that local antibodies play a subordinate role in host protection against chlamydial infection. Immunohistochemical analysis of frozen sections of the genital tract revealed many CD4+ T cells in the IFN-gammaR-/- mice, with a dominance of interleukin 4-containing cells in mice following resolution of the secondary infection. However, in contrast to the findings with wild-type mice, the typical clusters of CD4+ T cells were not found in the IFN-gammaR-/- mice. Few and similarly distributed CD8+ T cells were observed in IFN-gammaR-/- and wild-type mice. Whereas chlamydia-infected macrophages from wild-type mice had no inclusion bodies (IB) and produced significant amounts of nitric oxide (NO) in the presence of IFN-gamma, macrophages from IFN-gammaR-/- mice contained many IB but no NO. These results indicate that CD4+ Th1 cells and IFN-gamma, rather than local antibodies, are critical elements in host immune protection stimulated by a natural ascending C. trachomatis infection in the female genital tract.
Johansson
M
M
Department of Medical Microbiology and Immunology, University of Göteborg, Sweden.
Schön
K
K
Ward
M
M
Lycke
N
N
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D015703:Antigens, CD / Q000502:physiology*; D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis; D005260:Female; D005831:Genital Diseases, Female / Q000276:immunology*; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000502:physiology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D017471:Receptors, Interferon / Q000378:metabolism / Q000502:physiology*; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology; D000096743:Interferon gamma Receptor
D000907:Antibodies, Bacterial; D015703:Antigens, CD; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007371:Interferon-gamma; D009569:Nitric Oxide; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor