Host Regulators of Liver Fibrosis During Human Schistosomiasis

Kamdem, Séverin Donald; Moyou-Somo, Roger; Brombacher, Frank; Nono, Justin Komguep

doi:10.3389/fimmu.2018.02781

Cited by 84 publications

(93 citation statements)

References 105 publications

(146 reference statements)

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“…Schistosomiasis is a chronic and potentially lethal disease, and the disease morbidity is caused by schistosome eggs and not directly by adult worms (35). Liver fibrosis caused by S. mansoni and S. japonicum is one of the most severe complications in advanced schistosomiasis, which usually accompanies portal hypertension and hepatosplenomegaly, and sometimes it is fatal (36).…”

Section: Discussionmentioning

confidence: 99%

Galectins, Eosinophiles, and Macrophages May Contribute to Schistosoma japonicum Egg-Induced Immunopathology in a Mouse Model

Huang

Zhang

et al. 2020

Front. Immunol.

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Schistosomiasis is a severe public health problem, which can cause tissue fibrosis and can even be fatal. Previous studies have proven that galectins and different kinds of cells involve in the regulation of tissue fibrosis process. In this study, outbred Kunming mice were infected with Schistosoma japonicum (S. japonicum). Our results showed that compared with uninfected mice, there were severe egg granulomatous inflammation and tissue fibrosis in the livers, spleens, and large intestines of S. japonicum-infected mice at 8 weeks post-infection (p.i.), and the number of eosinophils by hematoxylin and eosin staining and CD68 macrophage-positive area by immunohistochemical staining were significantly increased. Detected by using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), at 8 weeks after S. japonicum infection, the mRNA expression levels of galectin (Gal)-1, Gal-3, CD69, eosinophil protein X (EPX), and chitinase 3-like protein 3 (Ym1) were significantly increased in liver, spleen, and large intestine; eotaxin-1 (CCL11) and eosinophil cationic protein were significantly increased in both liver and spleen; eotaxin-2 (CCL24) and Arginase1 (Arg1) were significantly increased in both spleen and large intestine; and CD200R was significantly increased in both liver and large intestine. However, interleukin (IL)-1ß and inducible nitric oxide synthase (iNOS) were only significantly increased in liver. The M2/M1 ratio of CD200R/CD86 genes was significantly increased in liver, and ratios of Ym1/IL-1β and Ym1/iNOS were significantly increased in liver, spleen, and large intestine of S. japonicum-infected mice. Ex vivo study further confirmed that the levels of Gal-1, Gal-3, CD200R, Arg1, and Ym1 were significantly increased, and the ratios of CD200R/CD86 and Ym1/IL-1β were significantly increased in peritoneal macrophages isolated from S. japonicum-infected mice at 8 weeks p.i. In addition, correlation analysis showed that significant positive correlations existed between mRNA levels of Gal-1/Gal-3 and EPX in liver, between Gal-3 and Ym1 in both liver and large intestine, and between Gal-3 and CD200R in peritoneal macrophages of S. japonicum-infected mice. Our data suggested that Gal-1, Gal-3, eosinophils, and macrophages are likely involved in the development of egg granulomatous response and fibrosis induced by S. japonicum infection.

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Section: Discussionmentioning

confidence: 99%

Galectins, Eosinophiles, and Macrophages May Contribute to Schistosoma japonicum Egg-Induced Immunopathology in a Mouse Model

Huang

Zhang

et al. 2020

Front. Immunol.

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“…Schistosomiasis is a widespread parasitic disease and affects more than 200 million people in many developing countries in tropical and subtropical areas [1]. The schistosome egg-induced hepatic granulomatous response, which subsequently results in serious liver fibrosis, is central to the morbidity and mortality in patients with schistosomiasis [2]. Thus, the effective suppression of granulomatous response-trigger liver fibrosis is crucial for schistosomiasis treatment.…”

Section: Introductionmentioning

confidence: 99%

hUCMSC-extracellular vesicles downregulated hepatic stellate cell activation and reduced liver injury in S. japonicum-infected mice

Dong

Chen

et al. 2020

Stem Cell Res Ther

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Background: Accumulating evidence shows that mesenchymal stem cells (MSCs) have the potential as a cellular therapy avenue for schistosome-induced liver injury. Extracellular vesicles (EVs) are membranous vesicles released by almost all cell types, and EVs produced by MSCs (MSC-EVs) exert therapeutic effects in several disease models. However, the potential of MSC-EVs in schistosomiasis treatment remains unclear. Methods: Using survival analysis, HE and Masson's trichrome staining, immunohistochemical, western blot analysis, real-time PCR, and EdU proliferation, we investigated the effects of human umbilical cord MSC-derived EVs (hUCMSC-EVs) on the survival and liver injury in the S. japonicum-infected mice and explored the underlying mechanism. Results: Here, we found that like hUCMSCs, hUCMSC-EVs significantly ameliorated liver injury and improved the survival of schistosome-infected mice. Indeed, the hUCMSC-EV-mediated alleviation of liver injury is associated with decreased expression of α-smooth muscle actin (α-SMA), collagen 1, and collagen 3. More importantly, we showed that hUCMSC-EVs directly suppressed the proliferation of LX2 (human hepatic stellate cell) in vitro. In addition, hUCMSC-EVs significantly downregulated the activation of LX2 after transforming growth factor-β1 (TGF-β1) treatment. Conclusion: Our results provided the first evidence that hUCMSC-EVs reduced liver injury in S. japonicum-infected mice, potentially creating new avenues for the treatment of liver damage in schistosomiasis.

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“…Both in vivo and clinical studies focusing on S. japonicum infections revealed that hepatic stellate cells (HSCs) are the key drivers of hepatic brosis [35,37], via collagen production and deposition. Importantly, liver brosis presentations have the potential to evolve into liver cirrhosis or liver cancer in the future [38]. Several studies have assessed the role of gut microbiota in cirrhosis of different etiologies [11,16,39,40,41].…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota signatures in Schistosoma japonicum infection-induced liver cirrhosis patients

Gui

Zhu

Xiao

et al. 2020

Preprint

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Background: One of the serious complications induced by Schistosoma japonicum infection is the development of liver cirrhosis. Several studies have assessed the role of gut microbiota in cirrhosis of different etiologies, but none has done so in the context of S. japonicum infection in humans. Here, to explore the possible role of gut microbiota in S. japonicum infection-induced liver cirrhosis, we conducted an observational clinical study.Methods: Twenty-four patients with S. japonicum infection-induced liver cirrhosis and 25 age- and gender-matched controls from Zhejiang Province, China, were enrolled in the study. Fecal samples were collected and used for 16S rRNA gene hypervariable V4 region Illumina MiSeq sequencing.Results: Eight hundred seven operational taxonomic units (OTUs) were detected, of which 491 were common in the two groups, while 123 and 193 were unique for the control and cirrhosis groups, respectively. Overall, no significant differences in both alpha and beta diversities and overall microbiota structure were found in the two groups. However, Bacilli (Class) and Lactobacillales (Order) were significantly higher in patients with S. japonicum infection-induced liver cirrhosis than in healthy individuals.Conclusions: Altogether, our results suggest that the gut microbiota of S. japonicum infection-induced liver cirrhosis patients is similar to that of healthy individuals.

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Host Regulators of Liver Fibrosis During Human Schistosomiasis

Cited by 84 publications

References 105 publications

Galectins, Eosinophiles, and Macrophages May Contribute to Schistosoma japonicum Egg-Induced Immunopathology in a Mouse Model

Galectins, Eosinophiles, and Macrophages May Contribute to Schistosoma japonicum Egg-Induced Immunopathology in a Mouse Model

hUCMSC-extracellular vesicles downregulated hepatic stellate cell activation and reduced liver injury in S. japonicum-infected mice

Gut microbiota signatures in Schistosoma japonicum infection-induced liver cirrhosis patients

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