3 years ago

Transcervical inoculation with Chlamydia trachomatis induces infertility in HLA-DR4-transgenic and wild type mice.

Delia F Tifrea, Sukumar Pal, Luis M de la Maza, Guangming Zhong
Chlamydia trachomatis (Ct) is the leading cause of infection-induced infertility in women. Attempts to control this epidemic with screening programs and antibiotic therapy have failed. Currently, a vaccine to prevent Ct infections is not available. In order to develop an animal model for evaluating vaccine antigens that can be applied to humans, we used Ct serovar D (strain UW-3/Cx) (Ct-D) to induce infertility in mice whose major histocompatibility complex class II antigen was replaced with the human leukocyte antigen (HLA)-DR4. Transcervical inoculation, of medroxy-progesterone-treated HLA-DR4 transgenic mice, with 5 x 10(5)Ct-D inclusion forming units (IFUs) induced a significant reduction in fertility with a mean number of embryos/mouse of 4.4 ± 1.3 compared to 7.8 ± 0.5 for the uninfected control mice (P < 0.05). A similar fertility reduction was elicited in the wild type (WT) C57BL/6 mice (4.3 ± 1.4) when compared to the WT controls (9.1 ± 7.8) (P < 0.05). Following infection WT mice mounted more robust humoral and cellular immune responses than HLA-DR4 mice. As determined by vaginal shedding HLA-DR4 mice were more susceptible to a transcervical Ct-D infection compared to WT mice. To determine if HLA-DR4 transgenic and WT mice could be protected by vaccination, 10(4) IFU of Ct-D were delivered intranasally and mice challenged transcervically six-weeks later with 5 x 10(5)Ct-D IFUs. As determined by severity and length of vaginal shedding, WT C57BL/6 and HLA-DR4 mice were significantly protected by vaccination. The advantages and limitations of the HLA-DR4 transgenic mouse model for evaluating human Ct vaccine antigens are discussed.

Publisher URL: http://doi.org/10.1128/IAI.00722-17

DOI: 10.1128/IAI.00722-17

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