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

Helene L. E. Midttun, Nathalie Acevedo, Per Skallerup, Sara Almeida, Kerstin Skovgaard, Lars Andresen, Søren Skov, Luis Caraballo, Irma van Die, Claus B. Jørgensen, Merete Fredholm, Stig M. Thamsborg, Peter Nejsum, Andrew R. Williams*

*Corresponding author for this work

    Research output: Contribution to journalJournal articleResearchpeer-review

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    Abstract

    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
    JournalJournal of Infectious Diseases
    Volume217
    Issue number2
    Pages (from-to)310-319
    ISSN0022-1899
    DOIs
    Publication statusPublished - 2018

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