Ascaris Suum Infection Downregulates Inflammatory Pathways in the Pig Intestine In Vivo and in Human Dendritic Cells In Vitro

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DOI

  • Helene L E Midttun, University of Copenhagen
  • ,
  • Nathalie Acevedo, Institute for Immunological Research, University of Cartagena, Colombia.
  • ,
  • Per Skallerup, University of Copenhagen
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  • Sara Almeida, University of Copenhagen
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  • Kerstin Skovgaard, Section for Immunology and Vaccinology, Technical University of Denmark, Kongens Lyngby, Denmark.
  • ,
  • Lars Andresen, University of Copenhagen
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  • Søren Skov, University of Copenhagen
  • ,
  • Luis Caraballo, Institute for Immunological Research, University of Cartagena, Colombia.
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  • Irma van Die, Department of Molecular Cell Biology and Immunology, VU University Medical Centre, Amsterdam, The Netherlands.
  • ,
  • Claus B Jørgensen
  • Merete Fredholm, University of Copenhagen
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  • Stig M Thamsborg, University of Copenhagen
  • ,
  • Peter Nejsum
  • Andrew R Williams, University of Copenhagen

Ascaris suum is a helminth parasite of pigs closely related to its human counterpart, A. lumbricoides, which infects almost 1 billion people. Ascaris is thought to modulate host immune and inflammatory responses, which may drive immune hyporesponsiveness during chronic infections. Using transcriptomic analysis, we show here that pigs with a chronic A. suum infection have a substantial suppression of inflammatory pathways in the intestinal mucosa, with a broad downregulation of genes encoding cytokines and antigen-processing and costimulatory molecules. A. suum body fluid (ABF) suppressed similar transcriptional pathways in human dendritic cells (DCs) in vitro. DCs exposed to ABF secreted minimal amounts of cytokines and had impaired production of cyclooxygengase-2, altered glucose metabolism, and reduced capacity to induce interferon-gamma production in T cells. Our in vivo and in vitro data provide an insight into mucosal immune modulation during Ascaris infection, and show that A. suum profoundly suppresses immune and inflammatory pathways.

Original languageEnglish
JournalThe Journal of Infectious Diseases
Volume217
Issue2
Pages (from-to)310-319
Number of pages10
ISSN0022-1899
DOIs
Publication statusPublished - 4 Jan 2018

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