Genital tract lesions in sexually mature Göttingen minipigs during the initial stages of experimental vaginal infection with Chlamydia trachomatis serovar D

Abstract

BackgroundChlamydia is one of the most common sexually transmitted diseases in humans worldwide, causing chronic lesions in the reproductive tract. Due to its often asymptomatic course, there is limited knowledge about the initial changes in the genital tract following infection. This study employs a novel sexually mature minipig model to investigate the initial histopathological changes following vaginal infection with Chlamydia trachomatis serovar D.ResultsA vaginal inoculation resulted in an infection primarily affecting the lower genital tract. The histopathological changes were characterized by a subepithelial inflammation consisting of neutrophils and mononuclear cells, followed by an increase in the number of plasma cells within the sub-epithelial stroma of the vagina. Detection of Chlamydia was associated with expression of cyclooxygenase-2 and interleukin-8 by superficial epithelial cells. The infection was self-limiting, with a duration of 7 days.ConclusionNeutrophils, plasma cells and IL-8 have been linked with Chlamydia genital infection of unknown duration in human patients. In this study, we observe a similar pattern of local immune response/inflammation following experimental inoculation suggesting this porcine model shows promise as a model for translational chlamydia research.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-016-0793-6) contains supplementary material, which is available to authorized users.

Contribution of the swine model in the study of human sexually transmitted infections

“…expression (Erneholm et al, 2016). Similar rapid clearance was observed in non-vaccinated control minipigs inoculated with either 3.9 × 10 9 IFUs (Bøje et al, 2016) or 5 × 10 9 IFUs (Lorenzen et al, 2015a) as part of vaccination studies.…”

“…Intrauterine inoculation via laparotomy during estrus was short (up to 5 days) and self-curing but during diestrus this infection induced a long-term infection until the end of the study (10 days). This difference can be explained by the higher activity of the uterine mucosal innate immune system of pigs during estrus (Erneholm et al, 2016;Lorenzen et al, 2015b).…”

“…In an attempt to establish a longer lasting infection by inoculating the bacteria at a site where columnar epithelial cells were present, Lorenzen et al (Lorenzen et al, 2017) performed intrauterine inoculation during laparotomy using a dose of either 1 x10 5 or 1 x 10 8 IFUs as well as a transcervical challenge using a dose of 1 x 10 9 IFUs. The rationale behind inoculation directly into the uterine lumen was the absence of columnar epithelial cells in the vagina and cervix of minipigs and the longer cervical canal with mucosal folds, which may have prevented sufficient numbers of bacteria to have reached the uterine mucosa in the previous studies (Bøje et al, 2016;Erneholm et al, 2016;Lorenzen et al, 2015a). The transcervical challenge during estrus induced an infection in all (8/8) inoculated animals up to seven days post inoculation.…”

Genital Infiltrations of CD4+ and CD8+ T Lymphocytes, IgA+ and IgG+ Plasma Cells and Intra-Mucosal Lymphoid Follicles Associate With Protection Against Genital Chlamydiatrachomatis Infection in Minipigs Intramuscularly Immunized With UV-Inactivated Bacteria Adjuvanted With CAF01

“…The vaginal swabs for q-PCR detection were treated slightly differently in the two separate experiments, however, all samples from day 3 pi were treated similarly: DNA extraction was performed with Chelex ® 100 (Bio-Rad, Life Science, Denmark) and real-time q-PCR detection of C. trachomatis was performed by detection of the 16S rRNA gene as described in (Bøje et al, 2015; Erneholm et al, 2016). Based on the negative control, the C t cut-off for true positive samples was determined to be 37.…”

The Complexity of Interactions Between Female Sex Hormones and Chlamydia trachomatis Infections

“…To evaluate C. trachomatis infection in mice, the animals must be inoculated transcervically, bypassing natural ascension of the pathogen to the upper FGT from an initial cervical infection. Likewise, Göttingen minipigs must be transcervically inoculated with C. trachomatis during estrus to establish a lasting infection (>5 days) [37][38][39]. Intrauterine inoculation of minipigs with C. trachomatis during diestrus produces the longest duration of infection (≥10 days).…”