Myricetin Possesses Anthelmintic Activity and Attenuates Hepatic Fibrosis via Modulating TGFβ1 and Akt Signaling and Shifting Th1/Th2 Balance in Schistosoma japonicum-Infected Mice

Huang, Ping; Zhou, Ming; Cheng, Shaoyun; Hu, Yue; Gao, Minzhao; Ma, Yu-Bin; Limpanont, Yanin; Zhou, Hongli; Dekumyoy, Paron; Cheng, Yixin; Lv, Ziquan

doi:10.3389/fimmu.2020.00593

Cited by 46 publications

(30 citation statements)

References 52 publications

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“…Shifts in the Th1 response to the Th2 response are a determining factor in the mechanism of granuloma formation and hepatic fibrosis ( Bourke et al, 2013 ; Qiu et al, 2017 ; Romano et al, 2016 ). Targeting the Th1/Th2 balance in S. japonicum –infected mice can attenuate hepatic fibrosis ( Huang et al, 2020 ). Furthermore, a schistosome infection can also cause a wide range of clinical symptoms such as gut inflammation and affect the gut microbiota of mice ( Hu et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Bacillus subtilis Attenuates Hepatic and Intestinal Injuries and Modulates Gut Microbiota and Gene Expression Profiles in Mice Infected with Schistosoma japonicum

Lin

Song

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Parasitic infection can induce pathological injuries and impact the gut microbiota diversity and composition of the host. Bacillus subtilis is a nonpathogenic and noninvasive probiotic bacterium for humans and other animals, playing an important role in improving the host immune system’s ability to respond to intestinal and liver diseases and modulating gut microbiota. However, whether B. subtilis can impact biological functions in Schistosoma japonicum–infected mice is unclear. This study used oral administration (OA) of B. subtilis to treat mice infected with S. japonicum. We evaluated changes in the gut microbiota of infected mice using 16 S rRNA gene sequencing and differentially expressed gene profiles using transcriptome sequencing after OA B. subtilis. We found that OA B. subtilis significantly attenuated hepatic and intestinal pathological injuries in infected mice. The gut microbiota of mice were significantly altered after S. japonicum infection, while OA B. subtilis remodel the diversity and composition of gut microbiomes of infected mice. We found that the S. japonicum–infected mice with OA B. subtilis had an overabundance of the most prevalent bacterial genera, including Bacteroides, Enterococcus, Lactobacillus, Blautia, Lachnoclostridium, Ruminiclostridium, and Enterobacter. Transcriptomic analysis of intestinal tissues revealed that OA B. subtilis shaped the intestinal microenvironment of the host responding to S. japonicum infection. Differentially expressed genes were classified into KEGG pathways between S. japonicum–infected mice and those without included cell adhesion molecules, intestinal immune network for IgA production, hematopoietic cell lineage, Fc epsilon RI signaling pathway, Th1 and Th2 cell differentiation, Th17 cell differentiation, calcium signaling pathway, Fc gamma R-mediated phagocytosis, chemokine signaling pathway, phospholipase D signaling pathway, NF-kappa B signaling pathway, B cell receptor signaling pathway, pancreatic secretion, and phagosome. In conclusion, our findings showed that OA B. subtilis alleviates pathological injuries and regulates gene expression, implying that B. subtilis supplementation may be a potential therapeutic strategy for schistosomiasis. Our study may highlight the value of probiotics as a beneficial supplementary therapy during human schistosomiasis, but further studies are needed.

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Section: Introductionmentioning

confidence: 99%

Bacillus subtilis Attenuates Hepatic and Intestinal Injuries and Modulates Gut Microbiota and Gene Expression Profiles in Mice Infected with Schistosoma japonicum

Lin

Song

Zhang

et al. 2021

Front. Cell Dev. Biol.

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“…The tendency between neutrophils and Th17 cells was consistent in the mice with Schistosomiasis [19] [20]. Yang Q et al identi ed that MDSCs in the spleen of C57BL/6 mice with 5-6wks of 40 ± 5 Sj cercariae infection were strikingly increased [4].Huang P et al [21] showed that Th2, Th17 and CD25 + Foxp3 + CD4 + T cells (Treg) but not Th1 signi cantly increased in the BALB/c mice spleen post 7wks of 30 ± 2 Sj cercariae infection. Tebeje BM et al [22]identi ed that 5wks of 34 Sj cercariae-infected splenic Th1 cells responded more highly to Sj adult worm antigen preparation (SWAP)compared to SEA.…”

Section: Discussionmentioning

confidence: 86%

Inhibition of COX-2 Ameliorates Murine Liver Schistosomiasis Japonica Through Splenic Cellular Immunoregulation

Zhang

Chen

et al. 2021

Preprint

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We have reported the positive association of cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) axis with liver fibrosis induced by Schistosoma japonicum (Sj) infection, and TLR4 signaling controlled this axis. However, how COX-2 regulated immune response during Sj infection is still unclear. Here we further studied the effect of COX-2 specific inhibitor-NS398 on liver granulomatous inflammation, fibrosis and explored the mechanisms via evaluating different immune cell during Sj infection.The results showed that NS398 significantly reduced the size of liver granuloma, spleen and mesenteric lymph node (MLN) and alleviated chronic granulomatous inflammation. Mechanically, it might be via decreasing the numbers of Sj-induced T helper type 1 (Th1), Th2, T follicular helper (Tfh), T follicular regulatory cells (Tfr) and germinal center B (GCB) cells to alleviate the liver inflammation and fibrosis. In addition, there were no difference of the numbers of macrophages, neutrophils, MDSCs,Th17 and total B cells in the spleen of the mice with or without NS-398 treatment. Our above data suggests that COX-2/PGE2 inhibition may represent a potential therapeutic approach to schistosomiasis japonica.

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“…Macrophages are classically divided into M1 and M2 macrophages, and different cell clusters have been detected for marker genes of M1 ( TNF , IL1B , IL12B ) and M2 ( ARG1 , TGFB1 , IL10 ). 3 , 21 TNF was expressed in MP(0), MP(4), MP(5) and MP(7). IL1B was expressed in all clusters except MP(2), MP(3) and MP(8).…”

Section: Resultsmentioning

confidence: 99%

“…1 One type of liver fibrosis, known as schistosomaassociated liver fibrosis, is induced by granulomatous inflammation around eggs deposited in the liver. 2,3 Schistosoma japonicum, S. mansoni and S. mekongi are the main species that will lead to schistosoma-associated liver fibrosis. 4 Importantly, extensive liver fibrosis results in portal hypertension, a leading cause of death in patients with schistosomiasis.…”

Section: Introductionmentioning

confidence: 99%

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A preliminary investigation into the immune cell landscape of schistosome‐associated liver fibrosis in humans

Zhou

et al. 2021

Immunol Cell Biol

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Schistosomiasis is a widespread helminth disease that poses a heavy social and economic burden on people worldwide. Advanced schistosomiasis often develops into schistosome-associated liver fibrosis, the pathogenesis of which remains unclear. This study aimed preliminarily to profile immune cells of schistosome-associated liver fibrosis using single-cell RNA sequencing. Three patient groups were enrolled, including an Schistosomiasis japonicum (SJ) group (n = 1), a chronic liver failure (CLF) group (n = 3) and a healthy control (HC) group (n = 2), revealing 17 cell clusters out of 20 093 cells. From these limited datasets, it was observed that T cell-1, mononuclear phagocytes(MP)-1 and dendritic cells (DCs) were higher in the SJ group. CAVIN2 + MP(2) was the predominant cell type in the MP subset of the SJ group (53%), and was higher than that in both the CLF (8%) and HC (1%) groups. Kupffer cell marker genes (CD163, MARCO and TIMD4) were enriched in caveolaeassociated protein 2 (CAVIN2) + MP(2), which was also an important source of TGFB1. The KEGG pathways of CAVIN2 + MP(2) indicated that they were associated with lysosome, endocytosis, phagosome and antigen processing and presentation. The preliminary study showed that granzyme B (GZMB) + T cell (1) and ankyrin repeat domain-containing protein 36B + T cell(3) were the most common T cells in the SJ group (50% and 32%, respectively). The KEGG pathways of GZMB + T cell(1) were mainly related to natural killer cellmediated cytotoxicity. The percentage of ring1 and YY1 binding protein (RYBP) + DC(1) was higher in the SJ group (57%) than in the CLF (16%) and HC (6%) groups. The KEGG pathway of RYBP + DC(1) was related to Fc gamma R-mediated phagocytosis and antigen processing and presentation. Overall, CAVIN2 + Kupffer cells were the main source of TGFB1, consisting primarily of mononuclear phagocytes in the livers of the SJ group subjects and potentially playing an irreplaceable role in hepatic fibrosis of schistosomiasis.

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Myricetin Possesses Anthelmintic Activity and Attenuates Hepatic Fibrosis via Modulating TGFβ1 and Akt Signaling and Shifting Th1/Th2 Balance in Schistosoma japonicum-Infected Mice

Abstract: the first direct evidence that myricin possesses potent anti-schistosome activities in vitro and in vivo, and offers new insights into the mechanisms of action by myricetin. The present findings suggest that myricetin could be further explored as a therapeutic agent for S. japonicum.

Cited by 46 publications

References 52 publications

Bacillus subtilis Attenuates Hepatic and Intestinal Injuries and Modulates Gut Microbiota and Gene Expression Profiles in Mice Infected with Schistosoma japonicum

Bacillus subtilis Attenuates Hepatic and Intestinal Injuries and Modulates Gut Microbiota and Gene Expression Profiles in Mice Infected with Schistosoma japonicum

Inhibition of COX-2 Ameliorates Murine Liver Schistosomiasis Japonica Through Splenic Cellular Immunoregulation

A preliminary investigation into the immune cell landscape of schistosome‐associated liver fibrosis in humans

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