The Differential and Dynamic Progression of Hepatic Inflammation and Immune Responses During Liver Fibrosis Induced by Schistosoma japonicum or Carbon Tetrachloride in Mice

Song, Lun; Yin, Xin; Mu, Shasha; Li, Jia-Huang; Gao, Hong; Zhang, Ying; Dong, Panpan; Mei, Congjin; Hua, Zichun

doi:10.3389/fimmu.2020.570524

Cited by 20 publications

(17 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because there are various factors causing LF, and the pathogenesis and pathological process of different types of LF are different, the effects of macrophage polarization also vary. A study has shown that M1 macrophages and related pro-inflammatory cytokines are markedly increased in carbon tetrachloride (CCl 4 )-induced LF, whereas M2 macrophage polarization seems to predominate in schistosome infection-induced LF ( 194 ). Therefore, the inhibition of M1 and M2 macrophage polarization may respectively alleviate CCl 4 - and schistosome infection-induced LF.…”

Section: The Role Of Macrophage Polarization In Liver Diseasesmentioning

confidence: 99%

Macrophage Polarization and Its Role in Liver Disease

et al. 2021

View full text Add to dashboard Cite

Macrophages are important immune cells in innate immunity, and have remarkable heterogeneity and polarization. Under pathological conditions, in addition to the resident macrophages, other macrophages are also recruited to the diseased tissues, and polarize to various phenotypes (mainly M1 and M2) under the stimulation of various factors in the microenvironment, thus playing different roles and functions. Liver diseases are hepatic pathological changes caused by a variety of pathogenic factors (viruses, alcohol, drugs, etc.), including acute liver injury, viral hepatitis, alcoholic liver disease, metabolic-associated fatty liver disease, liver fibrosis, and hepatocellular carcinoma. Recent studies have shown that macrophage polarization plays an important role in the initiation and development of liver diseases. However, because both macrophage polarization and the pathogenesis of liver diseases are complex, the role and mechanism of macrophage polarization in liver diseases need to be further clarified. Therefore, the origin of hepatic macrophages, and the phenotypes and mechanisms of macrophage polarization are reviewed first in this paper. It is found that macrophage polarization involves several molecular mechanisms, mainly including TLR4/NF-κB, JAK/STATs, TGF-β/Smads, PPARγ, Notch, and miRNA signaling pathways. In addition, this paper also expounds the role and mechanism of macrophage polarization in various liver diseases, which aims to provide references for further research of macrophage polarization in liver diseases, contributing to the therapeutic strategy of ameliorating liver diseases by modulating macrophage polarization.

show abstract

Section: The Role Of Macrophage Polarization In Liver Diseasesmentioning

confidence: 99%

Macrophage Polarization and Its Role in Liver Disease

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Many types of immune cells are involved in the host immune response to S. japonicum infection, such as Th1, Th2, Th17 [ 15 – 17 ], Tfh [ 18 , 19 ], Treg cells [ 20 , 21 ], DCs [ 22 – 24 ] and γδ T cells [ 25 ]. Tfh cells are a fairly recently identified subset of CD4 + T cells that have a distinct gene expression profile and act independently of Th1, Th2 and Th17 cell lineages [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Granulocytic myeloid-derived suppressor cells inhibit T follicular helper cells during experimental Schistosoma japonicum infection

Zhang

Liu

et al. 2021

Parasites Vectors

View full text Add to dashboard Cite

Background CD4+ T helper (Th) cells play critical roles in both host humoral and cellular immunity against parasitic infection and in the immunopathology of schistosomiasis. T follicular helper (Tfh) cells are a specialized subset of Th cells involved in immunity against infectious diseases. However, the role of Tfh cells in schistosome infection is not fully understood. In this study, the dynamics and roles of Tfh cell regulation were examined. We demonstrated that granulocytic myeloid-derived suppressor cells (G-MDSC) can suppress the proliferation of Tfh cells. Methods The levels of Tfh cells and two other Th cells (Th1, Th2) were quantitated at different Schistosoma japonicum infection times (0,3, 5, 8, 13 weeks) using flow cytometry. The proliferation of Tfh cells stimulated by soluble egg antigen (SEA) and soluble worm antigen (SWA) in vivo and in vitro were analyzed. Tfh cells were co-cultured with MDSC to detect the proliferation of Tfh cells labelled by 5(6)-carboxyfluorescein diacetate N-succinimidyl ester. We dynamically monitored the expression of programmed cell death protein 1 (PD-1) on the surface of Tfh cells and programmed cell death ligand 1 (PD-L1) on the surface of MDSC at different infection times (0, 3, 5, 8 weeks). Naïve CD4+ T cells (in Tfh cell differentiation) were co-cultured with G-MDSC or monocytic MDSC in the presence, or in the absence, of PD-L1 blocking antibody. Results The proportion of Tfh cells among CD4+ T cells increased gradually with time of S. japonicum infection, reaching a peak at 8 weeks, after which it decreased gradually. Both SEA and SWA caused an increase in Tfh cells in vitro and in vivo. It was found that MDSC can suppress the proliferation of Tfh cells. The expression of PD-1 on Tfh cells and PD-L1 from MDSC cells increased with prolongation of the infection cycle. G-MDSC might regulate Tfh cells through the PD-1/PD-L1 pathway. Conclusions The reported study not only reveals the dynamics of Tfh cell regulation during S. japonicum infection, but also provides evidence that G-MDSC may regulate Tfh cells by PD-1/PD-L1. This study provides strong evidence for the important role of Tfh cells in the immune response to S. japonicum infection. Graphical abstract

show abstract

“…Some literature has shown that the percentage of M1 macrophages in abdominal cavity after S. japonicum infection began to rise at 3 weeks after infection and began to decline at 8 weeks after infection. M2 macrophages were activated through m1-to-m2 phenotype transformation and began to rise from 8 weeks, but with different tissues, there may be differences in activated macrophages, which mainly depends on the changes of cytokines ( Zhu et al., 2014 ; Song et al., 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Lipocalin 2 Is a Regulator During Macrophage Polarization Induced by Soluble Worm Antigens

Shen

Wang

Huang

et al. 2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Caused by schistosomes, the human schistosomiasis is a tropical zoonotic parasitic disease. Pathologically, it occurs most often in the intestines and the liver, the sites of Schistosoma japonicum egg accumulation. The parasites’ produced eggs cause the main pathology in patients. Deposited parasite eggs in the liver induce the production of multiple cytokines that mediate the immune response, which in turn leads to granulomatous responses and liver fibrosis. These impact the hosts’ quality of life and health status, resulting in severe morbidity and even mortality. In this study, differentially expressed genes (DEGs) between ordinary samples and three 6- week infected mice were mined from microarray analysis based on the limma package. In total, we excavated the differential expression LCN2 was exhibited high expressions profile in GSE59276, GSE61376 demonstrated the result. Furthermore, CIBERSORT suggested detailed analysis of the immune subtype distribution pattern. In vivo experiments like real-time quantitative PCR, immunohistochemical (IHC) staining, and immunofluorescence (IF) demonstrated the expressions of LCN2 was significantly upregulated in S. japonicum–infected mice liver tissues and located in macrophages. Previous studies have shown that macrophages act as the first line of defense during schistosome infection and are an important part of liver granuloma. We used S. japonicum soluble worm antigens (SWA) to induce RAW264.7 cells to construct an in vitro inflammatory model. The current study aimed to investigate whether the NF-κB signaling network is involved in LCN2 upregulation induced by SWA and whether LCN2 can promote M1 polarization of macrophages under SWA treatment. Our research work suggests that LCN2 is significant in the development of early infection caused by S. japonicum and is of great value for further exploration. Collectively, the findings indicated that SWA promoted the expression of LCN2 and promoted M1 polarization of macrophages via the upregulation of NF-κB signaling pathway. Our findings demonstrate that NF-κB/LCN2 is necessary for migration and phagocytosis of M1 macrophages in response to SWA infection. Our study highlights the essential role of NF-κB/LCN2 in early innate immune response to infection.

show abstract

The Differential and Dynamic Progression of Hepatic Inflammation and Immune Responses During Liver Fibrosis Induced by Schistosoma japonicum or Carbon Tetrachloride in Mice

Cited by 20 publications

References 57 publications

Macrophage Polarization and Its Role in Liver Disease

Macrophage Polarization and Its Role in Liver Disease

Granulocytic myeloid-derived suppressor cells inhibit T follicular helper cells during experimental Schistosoma japonicum infection

Lipocalin 2 Is a Regulator During Macrophage Polarization Induced by Soluble Worm Antigens

Contact Info

Product

Resources

About