Evaluation of the role of angiogenic factors in the pathogenesis of schistosomiasis

Shariati, F.; Pérez-Arellano, José-Luis; Carranza, Cristina; López‐Abán, Julio; Vicente, Belén; Arefi, Maryam; Muro, Antonio

doi:10.1016/j.exppara.2011.01.016

Cited by 25 publications

(25 citation statements)

References 20 publications

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“…In addition, we also observed that the CBA/2J strain presented a significantly higher granuloma affected surface compared with C57BL/6. The evaluation macroscopic granulomatous lesions are positively correlated with the intensity of infection and it is useful for evaluating S. mansoni experimental pathology (Shariati et al 2011). These results confirm that CBA/2J presented high grade of susceptibility against S. mansoni infection showing a high grade of hepatic damage (Rutitzky and Stadecker 2011).…”

Section: Discussionsupporting

confidence: 73%

Identifying phenotypes involved in susceptibility to Schistosoma mansoni infection in F1B6CBA mice

Villar

Vicente

Blanco-Gómez

et al. 2014

Acta Parasitologica

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Schistosomiasis is a disease with a strong genetic component influenced by socioeconomic and ecological factors. Epidemiological studies have identified several genetic regions involved in the schistosomiasis susceptibility. However, it is not well known what physiological traits are predisposing to the disease. The study of experimental infections in inbred mouse strains with variable genetic susceptibility to the disease offers a good opportunity to tackle this question. F1B6CBA hybrid between the most divergent strains was infected in order to characterize the immunophenotypes that correlate with the susceptibility of schistosomiasis disease in mice. Complete blood counts and immunophenotype were determined at 0, 3, 6, and 9 weeks post infection. Nine weeks after cercariae exposure, animals were perfused and worm recovery was assessed. A large number of hepatic lesions, a reduction in the eosinophil and basophil count in the acute phase of infection and the decreased number of monocytes, neutrophils and B-lymphocytes are phenotypes associated with increased susceptibility to S. mansoni infection.

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Section: Discussionsupporting

confidence: 73%

Identifying phenotypes involved in susceptibility to Schistosoma mansoni infection in F1B6CBA mice

Villar

Vicente

Blanco-Gómez

et al. 2014

Acta Parasitologica

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“…Congruent with chronic inflammation, the innate immunity-associated cytokine IL-1α was also persistently elevated (Figure 6A). Interestingly, serum levels of VEGF were increased in egg-injected mice, which may have promoted aberrant vasculogenesis and hematuria analogous to human disease [33]. Finally, serum levels of IgE, a quintessential Type 2-associated antibody isotype, were increased beginning at 14 days post egg injection relative to controls, and remain elevated through day 28 post-injection (Figure 6B).…”

Section: Resultsmentioning

confidence: 94%

A Novel Mouse Model of Schistosoma haematobium Egg-Induced Immunopathology

et al. 2012

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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.

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“…Some studies have linked VEGF with harmful effects in the state of hepatic granuloma and fibrosis and cirrhosis in patients and experimental animal models [37]–[38]. Consistently, application of an angiogenic inhibitorin an experimental murine model of S. mansoni resulted in reduced injury characterized by attenuated hepatic granuloma formation and fibrosis [15]. MCP-1can trigger migration of monocytes into the hepatic granuloma.…”

Section: Discussionmentioning

confidence: 87%

“…Besides, VEGF is an important signaling protein involved in both vasculogenesis and angiogenesis. To that effect, previous studies have demonstrated that VEGF also plays an important role in promoting granuloma formation and fibrosis in experimental schistosomiasis [14]–[15].…”

Section: Introductionmentioning

confidence: 95%

A Boswellic Acid-Containing Extract Ameliorates Schistosomiasis Liver Granuloma and Fibrosis through Regulating NF-κB Signaling in Mice

Miao

Chen

et al. 2014

PLoS ONE

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Boswellic acid (BA)-containing extracts such as BSE have anti-inflammatory and immunomodulatory activity. In chronic schistosomiasis, the hepatic granuloma and fibrosis induced by egg deposition in the liver is the most serious pathological manifestations. However, little is known regarding the role of BAs in Schistosoma japonicum (S. japonicum) egg-induced liver granuloma and fibrosis. In order to investigate the effect of a water-soluble complex preparation of BSE, BSE-CD, on S. japonicum egg-induced liver pathology, liver granuloma and fibrosis were induced by infecting C57BL/6 mice with 18–22 cercariae of S. japonicum. S. japonicum cercariae infected mice were injected with BSE-CD at the onset of egg granuloma formation (early phase BSE-CD treatment after 4 weeks infection) or after the formation of liver fibrosis (late phase BSE-CD treatment after 7 weeks infection). Our data show that treatment of infected mice with BSE-CD significantly reduced both the extent of hepatic granuloma and fibrosis. Consistent with an inhibition of NF-κB signaling as evidenced by reduced IκB kinase (IKK) activation, the mRNA expression of VEGF (vascular endothelial growth factor, VEGF), TNF-α (tumor necrosis factor-alpha TNF-α) and MCP-1 (monocyte chemotactic protein 1, MCP-1) was decreased. Moreover, immunohistochemical analysis (IHC) revealed that the content of α-SMA in liver tissue of BSE-CD treated mice was dramatically decreased. Our findings suggest that BSE-CD treatment attenuates S. japonicum egg-induced hepatic granulomas and fibrosis, at least partly due to reduced NF-κB signaling and the subsequently decreased expression of VEGF, TNF-α, and MCP-1. Suppression of the activation of hepatic stellate cells (HSC) may also be involved in the therapeutic efficacy of BSE-CD.

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Evaluation of the role of angiogenic factors in the pathogenesis of schistosomiasis

Cited by 25 publications

References 20 publications

Identifying phenotypes involved in susceptibility to Schistosoma mansoni infection in F1B6CBA mice

Identifying phenotypes involved in susceptibility to Schistosoma mansoni infection in F1B6CBA mice

A Novel Mouse Model of Schistosoma haematobium Egg-Induced Immunopathology

A Boswellic Acid-Containing Extract Ameliorates Schistosomiasis Liver Granuloma and Fibrosis through Regulating NF-κB Signaling in Mice

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