A Novel Mouse Model of Schistosoma haematobium Egg-Induced Immunopathology

Abstract

Schistosoma haematobium is the etiologic agent for urogenital schistosomiasis, a major source of morbidity and mortality for more than 112 million people worldwide. Infection with S. haematobium results in a variety of immunopathologic sequelae caused by parasite oviposition within the urinary tract, which drives inflammation, hematuria, fibrosis, bladder dysfunction, and increased susceptibility to urothelial carcinoma. While humans readily develop urogenital schistosomiasis, the lack of an experimentally-tractable model has greatly impaired our understanding of the mechanisms that underlie this important disease. We have developed an improved mouse model of S. haematobium urinary tract infection that recapitulates several aspects of human urogenital schistosomiasis. Following microinjection of purified S. haematobium eggs into the bladder wall, mice consistently develop macrophage-rich granulomata that persist for at least 3 months and pass eggs in their urine. Importantly, egg-injected mice also develop urinary tract fibrosis, bladder dysfunction, and various urothelial changes morphologically reminiscent of human urogenital schistosomiasis. As expected, S. haematobium egg-induced immune responses in the immediate microenvironment, draining lymph nodes, and systemic circulation are associated with a Type 2-dominant inflammatory response, characterized by high levels of interleukin-4, eosinophils, and IgE. Taken together, our novel mouse model may help facilitate a better understanding of the unique pathophysiological mechanisms of epithelial dysfunction, tissue fibrosis, and oncogenesis associated with urogenital schistosomiasis.

Tumour-like phenotypes in urothelial cells after exposure to antigens from eggs of Schistosoma haematobium: An oestrogen–DNA adducts mediated pathway?

“…Thus granulomata protect the host from toxic products of schistosome eggs. Despite the importance of this phenomenon in schistosomiasis mansoni, until recently (Fu et al, 2012), an informative model to analyse the issue in the context of S. haematobium SEA was not available. We aim to carry out studies in the future to address this issue.…”

“…Such a decline in the pattern of this infection suggests the importance of schistosome-associated bladder cancer that, elsewhere, may be more widespread than is presently thought (Shiff et al, 2010). In recent progress on the understanding of the host-parasite relationship of schistosomiasis haematobia, a draft genome sequence for S. haematobium was reported (Young et al, 2012) and a mouse model of S. haematobium egg induced immuno-pathogenesis and fibrosis typically found in human urogenital schistosomiasis was described (Fu et al, 2012). It was recently reported that this schistosome is amenable to being cultured in vitro and transformed with nucleic acid probes.…”

Contribution of myeloid cell subsets to liver fibrosis in parasite infection

“…The main human-infecting species are S. mansoni (in Africa and South America) and S. japonicum (in South and East Asia), causing intestinal and hepatosplenic schistosomiasis, and S. haematobium (in Africa and Middle East), causing urinary schistosomiasis. The latter species accounts for nearly half of that number, but little is known about the mechanisms underlying its pathophysiology, primarily due to the lack of an experimentally tractable mouse model [15]. These parasites are responsible for the most common fibrotic disease that arises due to chronic inflammation and the scarring of (liver or bladder) tissue.…”

“…Here, we provide an overview of the mechanisms by which clinically important parasites -such as Schistosoma mansoni and S. japonicum, and hydatid cysts from Echinococcus multilocularis that localize primarily in the liverdrive liver fibrogenesis following their interaction with myeloid cell subsets. Other parasites, such as Trypanosoma cruzi , Taenia solium, Nippostrongylus brasiliensis and Schistosoma haematobium, inducing fibrosis in the heart, brain, lungs and bladder, respectively [9][10][11][12][13][14][15], and liver flukes, such as Clonorchis sinensis and Opisthorchis viverrini , causing bile periductal fibrosis, which increases the risk for cholangiocarcinoma [16][17][18][19][20], are not covered here, due to the marginal information on the phenotype, function and activation status of myeloid cells in these pathogenic processes.…”

Schistosomiasis of the abdominal cavity and infertility: a case report

“…In female genital organs, ovaries and fallopian tubes sometimes have high egg burdens, but the mean eggs burdens in autopsy series are low. Egg burdens of the uterus and vagina are even lower 2,3 . The aim of this study is to report a case of schistosomiasis of the abdominal cavity and infertility.…”