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House dust mite drives proinflammatory eicosanoid reprogramming and macrophage effector functions.

Allergy 74, 1090-1101 (2019)
Publishers Version online available 12/2020 Free by publisher Postprint online available 12/2019 Open Access Green as soon as is submitted to ZB.
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 D-2 and E-2) 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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Publication type Article: Journal article
Document type Scientific Article
Keywords Eicosanoids ; House Dust Mite ; Lc-ms ; Ms ; Macrophages ; Type 2 Inflammation; Lipid Mediators; Dendritic Cells; Leukotrienes; Monocytes; Biosynthesis; Metabolism; Generation; Induction; Immunity; Asthma
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