Abstract
BackgroundOver 112 million people worldwide are infected with Schistosoma haematobium, one of the most prevalent schistosome species affecting humans. Female genital schistosomiasis (FGS) occurs when S. haematobium eggs are deposited into the female reproductive tract by adult worms, which can lead to pelvic pain, vaginal bleeding, genital disfigurement and infertility. Recent evidence suggests co-infection with S. haematobium increases the risks of contracting sexually transmitted diseases such as HIV. The associated mechanisms remain unclear due to the lack of a tractable animal model. We sought to create a mouse model conducive to the study of immune modulation and genitourinary changes that occur with FGS.MethodsTo model FGS in mice, we injected S. haematobium eggs into the posterior vaginal walls of 30 female BALB/c mice. A control group of 20 female BALB/c mice were injected with uninfected LVG hamster tissue extract. Histology, flow cytometry and serum cytokine levels were assessed at 2, 4, 6, and 8 weeks post egg injection. Voiding studies were performed at 1 week post egg injection.ResultsVaginal wall injection with S. haematobium eggs resulted in synchronous vaginal granuloma development within 2 weeks post-egg injection that persisted for at least 6 additional weeks. Flow cytometric analysis of vaginal granulomata revealed infiltration by CD4+ T cells with variable expression of the HIV co-receptors CXCR4 and CCR5. Granulomata also contained CD11b+F4/80+ cells (macrophages and eosinophils) as well as CXCR4+MerTK+ macrophages. Strikingly, vaginal wall-injected mice featured significant urinary frequency despite the posterior vagina being anatomically distant from the bladder. This may represent a previously unrecognized overactive bladder response to deposition of schistosome eggs in the vagina.ConclusionWe have established a new mouse model that could potentially enable novel studies of genital schistosomiasis in females. Ongoing studies will further explore the mechanisms by which HIV target cells may be drawn into FGS-associated vaginal granulomata.
Highlights
An estimated 240 million humans worldwide have schistosomiasis, an infection by Schistosoma worms of various species [1]
Since the immune response is primarily directed against S. haematobium eggs, and not as prominently to other stages of the parasite lifecycle, we previously developed a mouse model of S. haematobium egg-induced bladder disease by direct injection of S. haematobium eggs into the mouse bladder wall [24]
Over 8 weeks, the egg-associated mixed inflammatory infiltrate expanded and organized into well-defined granulomata surrounded by peripheral eosinophils and neutrophils and containing a diffuse, peripheral lymphocytic infiltrate (Figures 2–5)
Summary
An estimated 240 million humans worldwide have schistosomiasis, an infection by Schistosoma worms of various species [1]. S. haematobium infection is postulated to cause dyspareunia, vaginal bleeding, pruritis, and giant granulomata that appear as tumors in the female genital tract [6]. These signs and symptoms are termed female genital schistosomiasis (FGS) [7]. Over 112 million people worldwide are infected with Schistosoma haematobium, one of the most prevalent schistosome species affecting humans. Female genital schistosomiasis (FGS) occurs when S. haematobium eggs are deposited into the female reproductive tract by adult worms, which can lead to pelvic pain, vaginal bleeding, genital disfigurement and infertility.
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