RESUMEN
The Chlamydia trachomatis plasmid and inclusion membrane protein CT135 are virulence factors in the pathogenesis of murine female genital tract infection. To determine if these virulence factors play a similar role in female nonhuman primates, we infected pig-tailed macaques with the same C. trachomatis strains shown to be important in the murine model. Wild-type C. trachomatis and its isogenic mutant strain deficient in both plasmid and CT135 were used to infect macaques. Macaques were given primary and repeated cervicovaginal challenges with the wild-type and mutant strains. The infection rate, infection duration, and antibody response were similar among macaques infected with both strains. Unexpectedly, colposcopy, laparoscopy, and histologic analysis revealed no substantial genital tract pathology following either primary or repeated cervicovaginal challenges. Cytokine analysis of cervicovaginal secretions from both challenged groups revealed low concentrations of interleukin 1ß (IL-1ß) and elevated levels of the interleukin 1 receptor agonist (IL-1RA). We propose that an imbalance of IL-1ß and IL-1RA in macaques is the reason for the mild inflammatory responses observed in infected urogenital tissues. Thus, understanding the pathobiology of chlamydial infection requires a better understanding of host epigenetic and chlamydial genetic factors. Our findings also have implications for understanding the high frequency of asymptomatic infections in humans.
Asunto(s)
Infecciones por Chlamydia/inmunología , Chlamydia trachomatis/genética , Chlamydia trachomatis/inmunología , Macaca/inmunología , Plásmidos/inmunología , Infecciones del Sistema Genital/inmunología , Factores de Virulencia/inmunología , Animales , Femenino , Humanos , Ratones , Plásmidos/genética , Factores de Virulencia/genéticaRESUMEN
Preclinical studies of topical microbicide products, using appropriate animal models for assessing the safety of repeated use are essential. The pig-tailed macaque (Macaca nemestrina) model has been used to assess the safety of vaginally and rectally applied topical microbicide products. The availability of sexually mature female pig-tailed macaques has become extremely restricted. Currently, M. fascicularis is more readily available, and was therefore evaluated as an alternative model for topical microbicide pre-clinical evaluation. Twenty sexually mature M. fascicularis were assessed for feasibility to mimic the established models. The rectal and cervicovaginal microenvironments of the M. fascicularis were determined to be similar to those of M. nemestrina and humans. The gross anatomy was significantly smaller than that of the pig-tailed macaque, such that colposcopic examinations and multiple biopsies would not be possible. Thus, the M. fascicularis may not be useful for vaginally applied topical microbicide safety studies yet adequate for assessing safety of rectally applied topical microbicide products.