GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE343nnn/GSE343197/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE343197GEOGSEfalseAlox15 restrains glycolysis to support M2 macrophage effector function during helminth immunity.Macrophage polarization by type-2 cytokines is central to anti-helminth immunity and tissue repair. While some hallmark changes in macrophages are well-characterized and associated with protection against helminths, it is still unclear how macrophages exert their anti-helminth effects. In this context, we investigated Arachidonate 15-lipoxygenase (Alox15), a lipoxygenase well known for its role in macrophage polarization in the context of metabolic diseases, and a hallmark of type-2 macrophage (M2) human polarization. We show that in the absence of Alox15, M2 cannot trap and kill helminths. Surprisingly, expression of M2 markers was normal despite a loss of function. Instead, we found a concomitant increase in pro-inflammatory responses due to an uncontrolled activation of glycolysis. We further show that activation of Peroxisome proliferator-activated receptor-delta (PPAR-δ) by lipids downstream of Docosapentaenoic acid (DPA) can restore normal glycolysis control, highlighting a novel role of lipids in the fine-tuning of the metabolic support required for optimal macrophage polarization.2026/08/17GSE343197GSM9947520GSM9947516GSM9947517GSM9947514GSM9947515GSM9947512GSM9947513GSM9947521GSM9947510GSM9947511GSM9947522GSM9947509GSM9947518GSM9947507GSM9947519GSM994750821103343197Mus musculus