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
Volume159
Issue number3
Pages (from-to)322-334
Number of pages13
ISSN0019-2805
DOIs
Publication statusPublished - 2020

Keywords

  • Ascaris suum
  • Dendritic cell
  • Type 2 immune response

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