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Updated: Aug 6, 2026

Assessing Anti-fungal Activity of Isolated Alveolar Macrophages by Confocal Microscopy
Published on: July 9, 2014
Macrophage-derived oxysterols organize T helper 2 cells to suppress type 1 inflammation during pulmonary fungal
Yufan Zheng1, Hannah E Dobson1,2, Makheni Jean Pierre1,3
1Molecular Mycology and Immunity Section, Laboratory of Host Immunity and Microbiome, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
Effective pulmonary immunity requires the precise spatial organization of immune cells, yet the mechanisms guiding their intratissue positioning during inflammation remain unclear. Here, we identify a cholesterol-derived chemotactic axis that spatially organizes T helper 2 (TH2) cells during fungal-induced pulmonary type 2 inflammation. Inflammation-expanded macrophages expressing cholesterol-25-hydroxylase (CH25H) produced 25-hydroxycholesterol, which was converted into the oxysterol 7α,25-dihydroxycholesterol to attract GPR183-expressing TH2 cells into infectious lesions. This TH2 cell positioning suppressed interferon-γ responsiveness in inflammatory Ly6C+ macrophages, promoting fungal persistence. Disruption of this axis via TH2-specific GPR183 deletion restored type 1 macrophage activation and enhanced fungal clearance. Our findings reveal a macrophage-driven, metabolite-based mechanism of immunosuppressive cell positioning in inflamed lung tissue.
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