Ascaris suum infection down-regulates inflammatory pathways in the pig intestine in vivo and in human dendritic cells in vitro
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Ascaris suum infection down-regulates inflammatory pathways in the pig intestine in vivo and in human dendritic cells in vitro. / Midttun, Helene L E; Acevedo, Nathalie; Skallerup, Per; Almeida, Sara; Skovgaard, Kerstin; Andresen, Lars; Skov, Søren; Caraballo, Luis; van Die, Irma; Jørgensen, Claus B; Fredholm, Merete; Thamsborg, Stig M; Nejsum, Peter; Williams, Andrew R.
In: The Journal of Infectious Diseases, Vol. 217, No. 2, 2018, p. 310-319.Research output: Contribution to journal › Journal article › Research › peer-review
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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: journals.permissions@oup.com.
PY - 2018
Y1 - 2018
N2 - Ascaris suum is a helminth parasite of pigs closely related to its human counterpart, A. lumbricoides, which infects almost one billion people. Ascaris spp. 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 down-regulation of genes encoding cytokines and antigen-processing and co-stimulatory molecules. A. suum body fluid (ABF) supressed 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 a reduced capacity to induce IFN-γ 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 one billion people. Ascaris spp. 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 down-regulation of genes encoding cytokines and antigen-processing and co-stimulatory molecules. A. suum body fluid (ABF) supressed 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 a reduced capacity to induce IFN-γ 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
VL - 217
SP - 310
EP - 319
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 2
ER -
ID: 185845779