IL-23 prevents IL-13-dependent tissue repair associated with Ly6C lo monocytes in Entamoeba histolytica -induced liver damage

Noll, Jill; Helk, Elena; Fehling, Helena; Bernin, Hannah; Marggraff, Claudia; Jacobs, Thomas; Huber, Samuel; Pelczar, Penelope; Ernst, Thomas; Ittrich, Harald; Otto, Benjamin; Mittrücker, Hans‐Willi; Hölscher, Christoph; Tacke, Frank; Bruchhaus, Iris; Tannich, Egbert; Lotter, Hannelore

doi:10.1016/j.jhep.2016.01.013

Cited by 21 publications

(19 citation statements)

References 38 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the mouse model for ALA, has some limitations regarding the artificial route of infection, it is well established [23–25] and allows in this study to discriminate between pathogenic and less pathogenic clones. Accordingly, the high reproducibility of the differences in the recovery time of the liver between „non-pathogenic”and „pathogenic” E .…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Differentially Expressed Genes Identified in Non-pathogenic and Pathogenic Entamoeba histolytica Clones Allow Identification of New Pathogenicity Factors Involved in Amoebic Liver Abscess Formation

et al. 2016

Self Cite

View full text Add to dashboard Cite

We here compared pathogenic (p) and non-pathogenic (np) isolates of Entamoeba histolytica to identify molecules involved in the ability of this parasite to induce amoebic liver abscess (ALA)-like lesions in two rodent models for the disease. We performed a comprehensive analysis of 12 clones (A1–A12) derived from a non-pathogenic isolate HM-1:IMSS-A and 12 clones (B1–B12) derived from a pathogenic isolate HM-1:IMSS-B. “Non-pathogenicity” included the induction of small and quickly resolved lesions while “pathogenicity” comprised larger abscess development that overstayed day 7 post infection. All A-clones were designated as non-pathogenic, whereas 4 out of 12 B-clones lost their ability to induce ALAs in gerbils. No correlation between ALA formation and cysteine peptidase (CP) activity, haemolytic activity, erythrophagocytosis, motility or cytopathic activity was found. To identify the molecular framework underlying different pathogenic phenotypes, three clones were selected for in-depth transcriptome analyses. Comparison of a non-pathogenic clone A1np with pathogenic clone B2p revealed 76 differentially expressed genes, whereas comparison of a non-pathogenic clone B8np with B2p revealed only 19 differentially expressed genes. Only six genes were found to be similarly regulated in the two non-pathogenic clones A1np and B8np in comparison with the pathogenic clone B2p. Based on these analyses, we chose 20 candidate genes and evaluated their roles in ALA formation using the respective gene-overexpressing transfectants. We conclude that different mechanisms lead to loss of pathogenicity. In total, we identified eight proteins, comprising a metallopeptidase, C2 domain proteins, alcohol dehydrogenases and hypothetical proteins, that affect the pathogenicity of E. histolytica.

show abstract

Section: Discussionmentioning

confidence: 99%

Overexpression of Differentially Expressed Genes Identified in Non-pathogenic and Pathogenic Entamoeba histolytica Clones Allow Identification of New Pathogenicity Factors Involved in Amoebic Liver Abscess Formation

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…At the age of 12–14 weeks male and female C57BL/6 mice were intrahepatically infected as previously described 31 , 66 with 2 × 10 5 in vitro-cultured E. histolytica trophozoites of the highly pathogenic clone B2, generated from the cell line B (HM-1:IMSS) 31 .…”

Section: Methodsmentioning

confidence: 99%

Androgens predispose males to monocyte-mediated immunopathology by inducing the expression of leukocyte recruitment factor CXCL1

et al. 2020

Self Cite

View full text Add to dashboard Cite

Hepatic amebiasis, predominantly occurring in men, is a focal destruction of the liver due to the invading protozoan Entamoeba histolytica. Classical monocytes as well as testosterone are identified to have important functions for the development of hepatic amebiasis in mice, but a link between testosterone and monocytes has not been identified. Here we show that testosterone treatment induces proinflammatory responses in human and mouse classical monocytes. When treated with 5α-dihydrotestosterone, a strong androgen receptor ligand, human classical monocytes increase CXCL1 production in the presence of Entamoeba histolytica antigens. Moreover, plasma testosterone levels of individuals undergoing transgender procedure correlate positively with the TNF and CXCL1 secretion from their cultured peripheral blood mononuclear cells following lipopolysaccharide stimulation. Finally, testosterone substitution of castrated male mice increases the frequency of TNF/CXCL1-producing classical monocytes during hepatic amebiasis, supporting the hypothesis that the effects of androgens may contribute to an increased risk of developing monocyte-mediated pathologies.

show abstract

“…cd T cells are the main source of IL-17 in many diseases, particularly in the early phases. 33,34 The IL-23/IL-17 axis plays an important role in experimental autoimmune encephalomyelitis, rheumatoid arthritis and inflammatory bowel disease models in mice. The IL-17 + cd T cells can promote IL-17 production from CD4 + T cells to amplify the loop of IL-17 production and exacerbate experimental autoimmune encephalomyelitis.…”

Section: Introductionmentioning

confidence: 99%

“…31,32 Interleukin-23 also promotes Th17 cell survival and IL-17A, IL-17F and IL-22 secretion. 33,34 The IL-23/IL-17 axis plays an important role in experimental autoimmune encephalomyelitis, rheumatoid arthritis and inflammatory bowel disease models in mice. 30,35,36 Our early research results have demonstrated that cd T cells, especially Vc4 cd T cells, can suppress the production of IFN-c by NKT cells by secreting IL-17A in Con A-induced liver injury.…”

Section: Introductionmentioning

confidence: 99%

γδ T cells are indispensable for interleukin‐23‐mediated protection against Concanavalin A‐induced hepatitis in hepatitis B virus transgenic mice

et al. 2017

View full text Add to dashboard Cite

Hepatitis B virus surface antigen (HBsAg) carriers are highly susceptible to liver injury triggered by environmental biochemical stimulation. Previously, we have reported an inverse correlation between γδ T cells and liver damage in patients with hepatitis B virus (HBV). However, whether γδ T cells play a role in regulating the hypersensitivity of HBsAg carriers to biochemical stimulation-induced hepatitis is unknown. In this study, using HBV transgenic (HBs-Tg) and HBs-Tg T-cell receptor-δ-deficient (TCR-δ ) mice, we found that mice genetically deficient in γδ T cells exhibited more severe liver damage upon Concanavalin A (Con A) treatment, as indicated by substantially higher serum alanine aminotransferase levels, further elevated interferon-γ (IFN-γ) levels and more extensive necrosis. γδ T-cell deficiency resulted in elevated IFN-γ in CD4 T cells but not in natural killer or natural killer T cells. The depletion of CD4 T cells and neutralization of IFN-γ reduced liver damage in HBs-Tg and HBs-Tg-TCR-δ mice to a similar extent. Further investigation revealed that HBs-Tg mice showed an enhanced interleukin-17 (IL-17) signature. The administration of exogenous IL-23 enhanced IL-17A production from Vγ4 γδ T cells and ameliorated liver damage in HBs-Tg mice, but not in HBs-Tg-TCR-δ mice. In summary, our results demonstrated that γδ T cells played a protective role in restraining Con A-induced hepatitis by inhibiting IFN-γ production from CD4 T cells and are indispensable for IL-23-mediated protection against Con A-induced hepatitis in HBs-Tg mice. These results provided a potential therapeutic approach for treating the hypersensitivity of HBV carriers to biochemical stimulation-induced liver damage.

show abstract

IL-23 prevents IL-13-dependent tissue repair associated with Ly6C lo monocytes in Entamoeba histolytica -induced liver damage

Cited by 21 publications

References 38 publications

Overexpression of Differentially Expressed Genes Identified in Non-pathogenic and Pathogenic Entamoeba histolytica Clones Allow Identification of New Pathogenicity Factors Involved in Amoebic Liver Abscess Formation

Overexpression of Differentially Expressed Genes Identified in Non-pathogenic and Pathogenic Entamoeba histolytica Clones Allow Identification of New Pathogenicity Factors Involved in Amoebic Liver Abscess Formation

Androgens predispose males to monocyte-mediated immunopathology by inducing the expression of leukocyte recruitment factor CXCL1

γδ T cells are indispensable for interleukin‐23‐mediated protection against Concanavalin A‐induced hepatitis in hepatitis B virus transgenic mice

Contact Info

Product

Resources

About