PuSH - Publication Server of Helmholtz Zentrum München

Ovezgeldiyev, D.* ; Trefzer, V.* ; Doolan, R.* ; Moyat, M.* ; Coakley, G.* ; Wickramasinghe, L.C.* ; Daunt, C.* ; Volpe, B.* ; Henkel, F. ; Serra, A.* ; Hartmann, M.* ; Rezaei, S.* ; Ubags, N.* ; Butler, A.* ; Chatzis, R.* ; Marsland, B.J.* ; Smith, A.A.T.* ; Deveson Lucas, D.* ; McGowan, E.N.S.* ; Binger, K.J.* ; McConville, M.J.* ; Esser-von Bieren, J. ; Harris, N.L.* ; Bouchery, T.*

Alox15 restrains glycolysis to support M2 macrophage effector function during helminth immunity.

J. Exp. Med. 223, DOI: 10.1084/jem.20241620 (2026)
DOI
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 (LOX) (Alox15), a LOX 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.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0022-1007
e-ISSN 1540-9538
Journal Journal of Experimental Medicine
Quellenangaben Volume: 223, Issue: 10 Pages: , Article Number: , Supplement: ,
Publisher Rockefeller University Press
Reviewing status Peer reviewed
Institute(s) Institute of Allergy Research (IAF)