Ascaris suum infection down-regulates inflammatory pathways in the pig intestine in vivo and in human dendritic cells in vitro

TY - JOUR

T1 - Ascaris suum infection down-regulates inflammatory pathways in the pig intestine in vivo and in human dendritic cells in vitro

AU - Midttun, Helene L E

AU - Acevedo, Nathalie

AU - Skallerup, Per

AU - Almeida, Sara

AU - Skovgaard, Kerstin

AU - Andresen, Lars

AU - Skov, Søren

AU - Caraballo, Luis

AU - van Die, Irma

AU - Jørgensen, Claus B

AU - Fredholm, Merete

AU - Thamsborg, Stig M

AU - Nejsum, Peter

AU - Williams, Andrew R

N1 - © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

PY - 2018/1/15

Y1 - 2018/1/15

N2 - 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.

AB - 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.

U2 - 10.1093/infdis/jix585

DO - 10.1093/infdis/jix585

M3 - Journal article

C2 - 29136163

SN - 0022-1899

VL - 217

SP - 310

EP - 319

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 2

ER -