House dust mite drives proinflammatory eicosanoid reprogramming and macrophage effector functions

Fiona D.R. Henkel, Antonie Friedl, Mark Haid, Dominique Thomas, Tiffany Bouchery, Pascal Haimerl, Marta de los Reyes Jiménez, Francesca Alessandrini, Carsten B. Schmidt-Weber, Nicola L. Harris, Jerzy Adamski, Julia Esser-von Bieren

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Eicosanoid lipid mediators play key roles in type 2 immune responses, for example in allergy and asthma. Macrophages represent major producers of eicosanoids and they are key effector cells of type 2 immunity. We aimed to comprehensively track eicosanoid profiles during type 2 immune responses to house dust mite (HDM) or helminth infection and to identify mechanisms and functions of eicosanoid reprogramming in human macrophages. Methods: We established an LC-MS/MS workflow for the quantification of 52 oxylipins to analyze mediator profiles in human monocyte-derived macrophages (MDM) stimulated with HDM and during allergic airway inflammation (AAI) or nematode infection in mice. Expression of eicosanoid enzymes was studied by qPCR and western blot and cytokine production was assessed by multiplex assays. Results: Short (24 h) exposure of alveolar-like MDM (aMDM) to HDM suppressed 5-LOX expression and product formation, while triggering prostanoid (thromboxane and prostaglandin D2 and E2) production. This eicosanoid reprogramming was p38-dependent, but dectin-2-independent. HDM also induced proinflammatory cytokine production, but reduced granulocyte recruitment by aMDM. In contrast, high levels of cysteinyl leukotrienes (cysLTs) and 12-/15-LOX metabolites were produced in the airways during AAI or nematode infection in mice. Conclusion: Our findings show that a short exposure to allergens as well as ongoing type 2 immune responses are characterized by a fundamental reprogramming of the lipid mediator metabolism with macrophages representing particularly plastic responder cells. Targeting mediator reprogramming in airway macrophages may represent a viable approach to prevent pathogenic lipid mediator profiles in allergy or asthma.

Original languageEnglish
Number of pages12
JournalAllergy
DOIs
Publication statusAccepted/In press - 1 Jan 2019

Keywords

  • eicosanoids
  • house dust mite
  • LC-MS/MS
  • macrophages
  • type 2 inflammation

Cite this

Henkel, F. D. R., Friedl, A., Haid, M., Thomas, D., Bouchery, T., Haimerl, P., ... Esser-von Bieren, J. (Accepted/In press). House dust mite drives proinflammatory eicosanoid reprogramming and macrophage effector functions. Allergy. https://doi.org/10.1111/all.13700
Henkel, Fiona D.R. ; Friedl, Antonie ; Haid, Mark ; Thomas, Dominique ; Bouchery, Tiffany ; Haimerl, Pascal ; de los Reyes Jiménez, Marta ; Alessandrini, Francesca ; Schmidt-Weber, Carsten B. ; Harris, Nicola L. ; Adamski, Jerzy ; Esser-von Bieren, Julia. / House dust mite drives proinflammatory eicosanoid reprogramming and macrophage effector functions. In: Allergy. 2019.
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abstract = "Background: Eicosanoid lipid mediators play key roles in type 2 immune responses, for example in allergy and asthma. Macrophages represent major producers of eicosanoids and they are key effector cells of type 2 immunity. We aimed to comprehensively track eicosanoid profiles during type 2 immune responses to house dust mite (HDM) or helminth infection and to identify mechanisms and functions of eicosanoid reprogramming in human macrophages. Methods: We established an LC-MS/MS workflow for the quantification of 52 oxylipins to analyze mediator profiles in human monocyte-derived macrophages (MDM) stimulated with HDM and during allergic airway inflammation (AAI) or nematode infection in mice. Expression of eicosanoid enzymes was studied by qPCR and western blot and cytokine production was assessed by multiplex assays. Results: Short (24 h) exposure of alveolar-like MDM (aMDM) to HDM suppressed 5-LOX expression and product formation, while triggering prostanoid (thromboxane and prostaglandin D2 and E2) production. This eicosanoid reprogramming was p38-dependent, but dectin-2-independent. HDM also induced proinflammatory cytokine production, but reduced granulocyte recruitment by aMDM. In contrast, high levels of cysteinyl leukotrienes (cysLTs) and 12-/15-LOX metabolites were produced in the airways during AAI or nematode infection in mice. Conclusion: Our findings show that a short exposure to allergens as well as ongoing type 2 immune responses are characterized by a fundamental reprogramming of the lipid mediator metabolism with macrophages representing particularly plastic responder cells. Targeting mediator reprogramming in airway macrophages may represent a viable approach to prevent pathogenic lipid mediator profiles in allergy or asthma.",
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Henkel, FDR, Friedl, A, Haid, M, Thomas, D, Bouchery, T, Haimerl, P, de los Reyes Jiménez, M, Alessandrini, F, Schmidt-Weber, CB, Harris, NL, Adamski, J & Esser-von Bieren, J 2019, 'House dust mite drives proinflammatory eicosanoid reprogramming and macrophage effector functions', Allergy. https://doi.org/10.1111/all.13700

House dust mite drives proinflammatory eicosanoid reprogramming and macrophage effector functions. / Henkel, Fiona D.R.; Friedl, Antonie; Haid, Mark; Thomas, Dominique; Bouchery, Tiffany; Haimerl, Pascal; de los Reyes Jiménez, Marta; Alessandrini, Francesca; Schmidt-Weber, Carsten B.; Harris, Nicola L.; Adamski, Jerzy; Esser-von Bieren, Julia.

In: Allergy, 01.01.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - House dust mite drives proinflammatory eicosanoid reprogramming and macrophage effector functions

AU - Henkel, Fiona D.R.

AU - Friedl, Antonie

AU - Haid, Mark

AU - Thomas, Dominique

AU - Bouchery, Tiffany

AU - Haimerl, Pascal

AU - de los Reyes Jiménez, Marta

AU - Alessandrini, Francesca

AU - Schmidt-Weber, Carsten B.

AU - Harris, Nicola L.

AU - Adamski, Jerzy

AU - Esser-von Bieren, Julia

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Eicosanoid lipid mediators play key roles in type 2 immune responses, for example in allergy and asthma. Macrophages represent major producers of eicosanoids and they are key effector cells of type 2 immunity. We aimed to comprehensively track eicosanoid profiles during type 2 immune responses to house dust mite (HDM) or helminth infection and to identify mechanisms and functions of eicosanoid reprogramming in human macrophages. Methods: We established an LC-MS/MS workflow for the quantification of 52 oxylipins to analyze mediator profiles in human monocyte-derived macrophages (MDM) stimulated with HDM and during allergic airway inflammation (AAI) or nematode infection in mice. Expression of eicosanoid enzymes was studied by qPCR and western blot and cytokine production was assessed by multiplex assays. Results: Short (24 h) exposure of alveolar-like MDM (aMDM) to HDM suppressed 5-LOX expression and product formation, while triggering prostanoid (thromboxane and prostaglandin D2 and E2) production. This eicosanoid reprogramming was p38-dependent, but dectin-2-independent. HDM also induced proinflammatory cytokine production, but reduced granulocyte recruitment by aMDM. In contrast, high levels of cysteinyl leukotrienes (cysLTs) and 12-/15-LOX metabolites were produced in the airways during AAI or nematode infection in mice. Conclusion: Our findings show that a short exposure to allergens as well as ongoing type 2 immune responses are characterized by a fundamental reprogramming of the lipid mediator metabolism with macrophages representing particularly plastic responder cells. Targeting mediator reprogramming in airway macrophages may represent a viable approach to prevent pathogenic lipid mediator profiles in allergy or asthma.

AB - Background: Eicosanoid lipid mediators play key roles in type 2 immune responses, for example in allergy and asthma. Macrophages represent major producers of eicosanoids and they are key effector cells of type 2 immunity. We aimed to comprehensively track eicosanoid profiles during type 2 immune responses to house dust mite (HDM) or helminth infection and to identify mechanisms and functions of eicosanoid reprogramming in human macrophages. Methods: We established an LC-MS/MS workflow for the quantification of 52 oxylipins to analyze mediator profiles in human monocyte-derived macrophages (MDM) stimulated with HDM and during allergic airway inflammation (AAI) or nematode infection in mice. Expression of eicosanoid enzymes was studied by qPCR and western blot and cytokine production was assessed by multiplex assays. Results: Short (24 h) exposure of alveolar-like MDM (aMDM) to HDM suppressed 5-LOX expression and product formation, while triggering prostanoid (thromboxane and prostaglandin D2 and E2) production. This eicosanoid reprogramming was p38-dependent, but dectin-2-independent. HDM also induced proinflammatory cytokine production, but reduced granulocyte recruitment by aMDM. In contrast, high levels of cysteinyl leukotrienes (cysLTs) and 12-/15-LOX metabolites were produced in the airways during AAI or nematode infection in mice. Conclusion: Our findings show that a short exposure to allergens as well as ongoing type 2 immune responses are characterized by a fundamental reprogramming of the lipid mediator metabolism with macrophages representing particularly plastic responder cells. Targeting mediator reprogramming in airway macrophages may represent a viable approach to prevent pathogenic lipid mediator profiles in allergy or asthma.

KW - eicosanoids

KW - house dust mite

KW - LC-MS/MS

KW - macrophages

KW - type 2 inflammation

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U2 - 10.1111/all.13700

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JO - Allergy

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