Animal Models for Studying Female Genital Tract Infection with Chlamydia trachomatis

Abstract

Chlamydia trachomatis is a Gram-negative obligate intracellular bacterial pathogen. It is the leading cause of bacterial sexually transmitted disease in the world, with more than 100 million new cases of genital tract infections with C. trachomatis occurring each year. Animal models are indispensable for the study of C. trachomatis infections and the development and evaluation of candidate vaccines. In this paper, the most commonly used animal models to study female genital tract infections with C. trachomatis will be reviewed, namely, the mouse, guinea pig, and nonhuman primate models. Additionally, we will focus on the more recently developed pig model. Chlamydia trachomatis, a Gram-negative obligate intracellular bacterium, is the leading cause of bacterial sexually transmitted disease. World Health Organization values for 2008 estimated an annual increase of over 100 million genital tract infections with C. trachomatis worldwide (1). The incidence of cases is increasing in many countries (1, 2). Genital tract infections with C. trachomatis can cause cervicitis in women and urethritis in men. However, these infections remain largely subclinical in approximately 70% of women and 50% of men and consequently are often not detected (3). Untreated infections may lead to pelvic inflammatory disease, tubal scarring, ectopic pregnancy, infertility, and chronic pelvic pain in women, epididymitis in men, and infant pneumonia in children (4-7). Uncomplicated chlamydial infections can be treated easily with antibiotics, but once infection and pathology are established, treatment may be less effective. Asymptomatic individuals can be identified through screening programs, but this approach is likely to be too costly for developing countries. A vaccination program would be much cheaper and have a greater impact in controlling C. trachomatis infections worldwide. Computer modeling suggests that even a partially efficacious chlamydial vaccination program would rapidly reduce the prevalence of genital infection (8). Animal models are indispensable for the study of C. trachomatis infections and the development and evaluation of candidate vaccines. Various animal models have been developed, including mouse (9, 10), guinea pig (11, 12), nonhuman primate (13,14), pig (15), rat (16), and rabbit (17) models. Here, the most commonly used animal models to study female genital tract infections with C. trachomatis will be reviewed, namely, the mouse, guinea pig, and nonhuman primate models. Additionally, we will focus on the more recently developed pig model. MOUSE MODELSMice are the most commonly used animals to study genital chlamydial infections. The advantages of the mouse model are their small size, ease of handling, availability in sufficient amounts, and low cost. Moreover, there are many well-characterized inbred and knockout mouse strains available (18). The female mouse genital tract is susceptible to infection with both Chlamydia muridarum (9) and C. trachomatis (10), which has resulted in the establishment of two murine mod...

Genital Chlamydia trachomatis: Understanding the Roles of Innate and Adaptive Immunity in Vaccine Research

“…C. muridarum is utilized for genital studies, because C. muridarum intravaginal infection closely mimics acute C. trachomatis infection in women. Moreover, it can cause hydrosalpinx, fibrosis, infertility, and abortion in mice (118)(119)(120)(121). C. muridarum genital infection is usually resolved in 3 to 4 weeks, and the mice are partially protected against subsequent reinfections (122,123).…”

“…C. trachomatis is also used, but the infection in mice is less severe and is resolved more quickly than C. muridarum infection. Additionally, a mouse C. trachomatis infection requires a larger number of infectious units (118) and usually causes pathology only when injected directly into the uterus, uterine horn, or ovarian bursa (92,124). However, C. trachomatis genital infection in women is mostly asymptomatic and often does not induce severe upper tract genital pathology.…”

“…ϩ T cells predominate in macaques after chlamydial infection (118). Although the macaque model is ideal for vaccine and immunology studies, the high cost and need for adequate facilities and expertise limit its use.…”

“…Advantages of this model include the ability to study chlamydial sexual transmission (male guinea pigs are able to be infected with Chlamydia) (131), the transmission of Chlamydia to newborns, and the fact that guinea pig genital tract infection is similar to that by C. trachomatis in humans. Additionally, the guinea pig is a good model for hormonal research because humans and guinea pigs have comparable estrous cycles (118,132,133). Studies have indicated that CD8 ϩ T cell genital infiltrates after infection are similar to those of humans and nonhuman primates (134,135).…”

Common Microflora Encountered in Reproductive Tract of Indigenous Pigs in Tamil Nadu, India

“…The secondary agents that are important include infection caused by Pasteurella multocida, Streptococcus suis, Actinobacillus suis (De Clercq et al, 2013;O'Meara et al, 2014). Abnormal vaginal microbiota is concerned with high risk of obstetrical and gynaecologic complications.…”