Fungal lipase LipA disarms macrophages by remodeling their lipidome, enabling full virulence in immunocompetent hosts.

Aspergillus fumigatus secreted lipase LipA is essential for full pathogenicity in immunocompetent hosts by actively remodeling macrophage lipidomes.

• Why it matters: Immunocompetent hosts can clear A. fumigatus, but how a fungal secreted factor disarms macrophages to enable virulence is unclear.
• What they did: LipA is enriched on conidial surfaces; macrophage exposure showed ΔlipA is phagocytosed more readily, with reduced conidial viability and pro-inflammatory cytokine production, and comparative lipidomics tracked LipA-driven lipid remodeling.
• The result: LipA depletes complex ether-linked phospholipids and PUFA reservoirs, promotes free fatty acid accumulation, limits phospholipase A2 substrates for pro-inflammatory eicosanoids, shifts ceramides toward sphingomyelins, and promotes macrophage survival, creating a permissive environment for fungal survival.

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