Fiona D R Henkel1, Antonie Friedl1, Mark Haid2, Dominique Thomas3, Tiffany Bouchery4,5, Pascal Haimerl1, Marta de Los Reyes Jiménez1, Francesca Alessandrini1, Carsten B Schmidt-Weber1, Nicola L Harris4,5, Jerzy Adamski2,6, Julia Esser-von Bieren1. 1. Center of Allergy and Environment (ZAUM), Technical University of Munich and Helmholtz Center Munich, Munich, Germany. 2. Institute of Experimental Genetics, Genome Analysis Center, Neuherberg, Germany. 3. Pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University Frankfurt, Frankfurt, Germany. 4. Laboratory of Intestinal Immunology, Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. 5. Department of Immunology and Pathology, Central Clinical School, Alfred Medical Research and Education Precinct, Monash University, Clayton, Victoria, Australia. 6. Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany.
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.
BACKGROUND:Eicosanoidlipid 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.
Authors: Saltanat Ualiyeva; Evan Lemire; Evelyn C Aviles; Caitlin Wong; Amelia A Boyd; Juying Lai; Tao Liu; Ichiro Matsumoto; Nora A Barrett; Joshua A Boyce; Adam L Haber; Lora G Bankova Journal: Sci Immunol Date: 2021-12-24
Authors: Luis Caraballo; Rudolf Valenta; Leonardo Puerta; Anna Pomés; Josefina Zakzuk; Enrique Fernandez-Caldas; Nathalie Acevedo; Mario Sanchez-Borges; Ignacio Ansotegui; Luo Zhang; Marianne van Hage; Eva Fernández; Luisa Arruda; Susanne Vrtala; Mirela Curin; Hans Gronlund; Antonina Karsonova; Jonathan Kilimajer; Ksenja Riabova; Daria Trifonova; Alexander Karaulov Journal: World Allergy Organ J Date: 2020-04-29 Impact factor: 4.084