Abstract
Historically, animal modeling of gonorrhea has been hampered by the exclusive adaptation of Neisseria gonorrhoeae to humans. Genital tract infection can be established in female mice that are treated with 17β-estradiol, however, and many features of experimental murine infection mimic human infection. Here we review the colonization kinetics and host response to experimental murine gonococcal infection, including mouse strain differences and evidence that IL-17 responses, toll-like receptor 4, and T regulatory cells play a role in infection. We also discuss the strengths and limitations of the mouse system and the potential of transgenic mice to circumvent host restrictions. Additionally, we review studies with genetically defined mutants that demonstrated a role for sialyltransferase and the MtrC–MtrD–MtrE active efflux pump in evading innate defenses in vivo, but not for factors hypothesized to protect against the phagocytic respiratory burst and H2O2-producing lactobacilli. Studies using estradiol-treated mice have also revealed the existence of non-host-restricted iron sources in the female genital tract and the influence of hormonal factors on colonization kinetics and selection for opacity (Opa) protein expression. Recent work by others with estradiol-treated mice that are transgenic for human carcinoembryonic adhesion molecules (CEACAMs) supports a role for Opa proteins in enhancing cellular attachment and thus reduced shedding of N. gonorrhoeae. Finally we discuss the use of the mouse model in product testing and a recently developed gonorrhea chlamydia coinfection model.
Highlights
The success of Neisseria gonorrhoeae (Gc) as a pathogen stems from the evolution of several sophisticated adaptation mechanisms that maintain its sole reservoir on the mucosae of infected humans
We review the colonization kinetics and host response to experimental murine gonococcal infection, including mouse strain differences and evidence that IL-17 responses, toll-like receptor 4, and T regulatory cells play a role in infection
We briefly discuss the use of this model in developing vaccines and vaginal microbicides against gonorrhea and describe a newly developed female mouse model of gonorrhea chlamydia coinfection for pathogenesis studies and developing products against pelvic inflammatory disease (PID)
Summary
The success of Neisseria gonorrhoeae (Gc) as a pathogen stems from the evolution of several sophisticated adaptation mechanisms that maintain its sole reservoir on the mucosae of infected humans Some of these mechanisms are sex-specific and in the case of female infection, their evolution appears to be shaped by hormonal influences. The use of estradioltreated mice as surrogate hosts for Gc has partially fulfilled the need for an animal model of Gc genital tract infection. The susceptibility of rodents to human genital tract pathogens is often linked to the estrous cycle and the use of steroid hormones to promote susceptiblity to Gc is consistent with other mouse models of sexually transmitted infections
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