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

24 Downloads (Pure)

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

Cite this

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. . / Ascaris Suum Infection Downregulates Inflammatory Pathways in the Pig Intestine In Vivo and in Human Dendritic Cells In Vitro. In: Journal of Infectious Diseases. 2018 ; Vol. 217, No. 2. pp. 310-319.
@article{cb5e4b5857694c29887198d7079d920a,
title = "Ascaris Suum Infection Downregulates Inflammatory Pathways in the Pig Intestine In Vivo and in Human Dendritic Cells In Vitro.",
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",
author = "Midttun, {Helene L. E.} and Nathalie Acevedo and Per Skallerup and Sara Almeida and Kerstin Skovgaard and Lars Andresen and S{\o}ren Skov and Luis Caraballo and {van Die}, Irma and J{\o}rgensen, {Claus B.} and Merete Fredholm and Thamsborg, {Stig M.} and Peter Nejsum and Williams, {Andrew R.}",
year = "2018",
doi = "10.1093/infdis/jix585",
language = "English",
volume = "217",
pages = "310--319",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "2",

}

Midttun, HLE, Acevedo, N, Skallerup, P, Almeida, S, Skovgaard, K, Andresen, L, Skov, S, Caraballo, L, van Die, I, Jørgensen, CB, Fredholm, M, Thamsborg, SM, Nejsum, P & Williams, AR 2018, 'Ascaris Suum Infection Downregulates Inflammatory Pathways in the Pig Intestine In Vivo and in Human Dendritic Cells In Vitro.', Journal of Infectious Diseases, vol. 217, no. 2, pp. 310-319. https://doi.org/10.1093/infdis/jix585

Ascaris Suum Infection Downregulates 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: Journal of Infectious Diseases, Vol. 217, No. 2, 2018, p. 310-319.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Ascaris Suum Infection Downregulates 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.

PY - 2018

Y1 - 2018

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

VL - 217

SP - 310

EP - 319

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 2

ER -