Body fluid from the parasitic worm Ascaris suum inhibits broad-acting pro-inflammatory programs in dendritic cells

Pankaj Arora, Janne Marie Moll, Daniel Andersen, Christopher Thomas Workman, Andrew R. Williams, Karsten Kristiansen, Susanne Brix*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Dendritic cells (DCs) are essential for generating T cell-based immune responses via sensing of potential inflammatory and metabolic cues in the local environment. However, there is still limited insight into the processes defining the end DC phenotype, including the type of early transcriptional changes in pro-inflammatory cues towards regulatory or type 2 immune-based cues induced by a variety of exogenous and endogenous molecules. Here, we compared the ability of a selected number of molecules to modulate the pro-inflammatory phenotype of lipopolysaccharide (LPS) and interferon-gamma (IFN-γ)-stimulated human monocyte-derived DCs towards an anti-inflammatory or regulatory phenotype, including Ascaris suum body fluid (helminth PCF), the metabolites succinate and butyrate and the type 2 cytokines TSLP and IL-25. Our data show that helminth PCF and butyrate treatment suppress the Th1-inducing pro-inflammatory DC phenotype through induction of different transcriptional programs in DCs. RNA sequencing indicated that helminth PCF treatment strongly inhibited the Th1 and Th17 polarizing ability of LPS+IFN-γ-matured DCs by downregulating myeloid differentiation primary response gene 88 (MyD88)-dependent and MyD88-independent pathways in TLR4 signaling. By contrast, butyrate treatment had a strong Th1-inhibiting action, while transcripts encoding important gut barrier defending factors such as IL18, IL1B and CXCL8 were upregulated. Collectively, our results further our understanding of how compounds from parasites and gut microbiota-derived butyrate may exert immunomodulatory effects on the host immune system.
Original languageEnglish
JournalImmunology
Number of pages33
ISSN0019-2805
DOIs
Publication statusAccepted/In press - 2019

Keywords

  • Ascaris suum
  • Dendritic cell
  • Type 2 immune respo

Cite this

@article{d5e589b83d7f45e5b275fc357d9c73a5,
title = "Body fluid from the parasitic worm Ascaris suum inhibits broad-acting pro-inflammatory programs in dendritic cells",
abstract = "Dendritic cells (DCs) are essential for generating T cell-based immune responses via sensing of potential inflammatory and metabolic cues in the local environment. However, there is still limited insight into the processes defining the end DC phenotype, including the type of early transcriptional changes in pro-inflammatory cues towards regulatory or type 2 immune-based cues induced by a variety of exogenous and endogenous molecules. Here, we compared the ability of a selected number of molecules to modulate the pro-inflammatory phenotype of lipopolysaccharide (LPS) and interferon-gamma (IFN-γ)-stimulated human monocyte-derived DCs towards an anti-inflammatory or regulatory phenotype, including Ascaris suum body fluid (helminth PCF), the metabolites succinate and butyrate and the type 2 cytokines TSLP and IL-25. Our data show that helminth PCF and butyrate treatment suppress the Th1-inducing pro-inflammatory DC phenotype through induction of different transcriptional programs in DCs. RNA sequencing indicated that helminth PCF treatment strongly inhibited the Th1 and Th17 polarizing ability of LPS+IFN-γ-matured DCs by downregulating myeloid differentiation primary response gene 88 (MyD88)-dependent and MyD88-independent pathways in TLR4 signaling. By contrast, butyrate treatment had a strong Th1-inhibiting action, while transcripts encoding important gut barrier defending factors such as IL18, IL1B and CXCL8 were upregulated. Collectively, our results further our understanding of how compounds from parasites and gut microbiota-derived butyrate may exert immunomodulatory effects on the host immune system.",
keywords = "Ascaris suum, Dendritic cell, Type 2 immune respo",
author = "Pankaj Arora and Moll, {Janne Marie} and Daniel Andersen and Workman, {Christopher Thomas} and Williams, {Andrew R.} and Karsten Kristiansen and Susanne Brix",
year = "2019",
doi = "10.1111/imm.13151",
language = "English",
journal = "Immunology",
issn = "0019-2805",
publisher = "Wiley-Blackwell",

}

Body fluid from the parasitic worm Ascaris suum inhibits broad-acting pro-inflammatory programs in dendritic cells. / Arora, Pankaj; Moll, Janne Marie; Andersen, Daniel; Workman, Christopher Thomas; Williams, Andrew R.; Kristiansen, Karsten; Brix, Susanne.

In: Immunology, 2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Body fluid from the parasitic worm Ascaris suum inhibits broad-acting pro-inflammatory programs in dendritic cells

AU - Arora, Pankaj

AU - Moll, Janne Marie

AU - Andersen, Daniel

AU - Workman, Christopher Thomas

AU - Williams, Andrew R.

AU - Kristiansen, Karsten

AU - Brix, Susanne

PY - 2019

Y1 - 2019

N2 - Dendritic cells (DCs) are essential for generating T cell-based immune responses via sensing of potential inflammatory and metabolic cues in the local environment. However, there is still limited insight into the processes defining the end DC phenotype, including the type of early transcriptional changes in pro-inflammatory cues towards regulatory or type 2 immune-based cues induced by a variety of exogenous and endogenous molecules. Here, we compared the ability of a selected number of molecules to modulate the pro-inflammatory phenotype of lipopolysaccharide (LPS) and interferon-gamma (IFN-γ)-stimulated human monocyte-derived DCs towards an anti-inflammatory or regulatory phenotype, including Ascaris suum body fluid (helminth PCF), the metabolites succinate and butyrate and the type 2 cytokines TSLP and IL-25. Our data show that helminth PCF and butyrate treatment suppress the Th1-inducing pro-inflammatory DC phenotype through induction of different transcriptional programs in DCs. RNA sequencing indicated that helminth PCF treatment strongly inhibited the Th1 and Th17 polarizing ability of LPS+IFN-γ-matured DCs by downregulating myeloid differentiation primary response gene 88 (MyD88)-dependent and MyD88-independent pathways in TLR4 signaling. By contrast, butyrate treatment had a strong Th1-inhibiting action, while transcripts encoding important gut barrier defending factors such as IL18, IL1B and CXCL8 were upregulated. Collectively, our results further our understanding of how compounds from parasites and gut microbiota-derived butyrate may exert immunomodulatory effects on the host immune system.

AB - Dendritic cells (DCs) are essential for generating T cell-based immune responses via sensing of potential inflammatory and metabolic cues in the local environment. However, there is still limited insight into the processes defining the end DC phenotype, including the type of early transcriptional changes in pro-inflammatory cues towards regulatory or type 2 immune-based cues induced by a variety of exogenous and endogenous molecules. Here, we compared the ability of a selected number of molecules to modulate the pro-inflammatory phenotype of lipopolysaccharide (LPS) and interferon-gamma (IFN-γ)-stimulated human monocyte-derived DCs towards an anti-inflammatory or regulatory phenotype, including Ascaris suum body fluid (helminth PCF), the metabolites succinate and butyrate and the type 2 cytokines TSLP and IL-25. Our data show that helminth PCF and butyrate treatment suppress the Th1-inducing pro-inflammatory DC phenotype through induction of different transcriptional programs in DCs. RNA sequencing indicated that helminth PCF treatment strongly inhibited the Th1 and Th17 polarizing ability of LPS+IFN-γ-matured DCs by downregulating myeloid differentiation primary response gene 88 (MyD88)-dependent and MyD88-independent pathways in TLR4 signaling. By contrast, butyrate treatment had a strong Th1-inhibiting action, while transcripts encoding important gut barrier defending factors such as IL18, IL1B and CXCL8 were upregulated. Collectively, our results further our understanding of how compounds from parasites and gut microbiota-derived butyrate may exert immunomodulatory effects on the host immune system.

KW - Ascaris suum

KW - Dendritic cell

KW - Type 2 immune respo

U2 - 10.1111/imm.13151

DO - 10.1111/imm.13151

M3 - Journal article

JO - Immunology

JF - Immunology

SN - 0019-2805

ER -