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<p>Granulomas are organized inflammatory lesions formed in response to persistent stimuli such as infections. Murine infection with <i>Leishmania donovani</i> results in granulomas in the liver, seeded by infected Kupffer cells, and serves as a well-defined model of infection-induced granuloma formation. The resolution of granulomatous inflammation requires dynamic shifts in immune-cell activation states, imposing metabolic demands. As mediators of cell signaling, lipid metabolism plays a key role in regulating inflammation and infection. How lipid changes are spatially linked to altered immune cell transcription remains unresolved. We performed a multimodal imaging analysis combining MALDI mass spectrometry, spatial and single cell transcriptomics, proteomics of flow-sorted macrophages and histopathology of <i>L. donovani</i> induced hepatic granulomas. Using this spatially-integrated approach, we identified LPCAT2-mediated membrane re-modelling of myeloid cells as a novel feature of these granulomas. Our study provides new insights into local immunometabolic changes associated with granuloma formation and macrophage activation.</p>

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Ontogeny independent expression of LPCAT2 in granuloma macrophages during experimental visceral leishmaniasis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月20日

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  • Shoumit Dey,
  • Jian-Hua Cao,
  • Benjamin Balluff,
  • Gaia Mazza,
  • Helen Ashwin,
  • Lesley Gilbert,
  • Sally James,
  • Adam A. Dowle,
  • Grant Calder,
  • Nidhi Sharma Dey,
  • Peter O’Toole,
  • Ron M. A. Heeren,
  • Paul M. Kaye

摘要

Granulomas are organized inflammatory lesions formed in response to persistent stimuli such as infections. Murine infection with Leishmania donovani results in granulomas in the liver, seeded by infected Kupffer cells, and serves as a well-defined model of infection-induced granuloma formation. The resolution of granulomatous inflammation requires dynamic shifts in immune-cell activation states, imposing metabolic demands. As mediators of cell signaling, lipid metabolism plays a key role in regulating inflammation and infection. How lipid changes are spatially linked to altered immune cell transcription remains unresolved. We performed a multimodal imaging analysis combining MALDI mass spectrometry, spatial and single cell transcriptomics, proteomics of flow-sorted macrophages and histopathology of L. donovani induced hepatic granulomas. Using this spatially-integrated approach, we identified LPCAT2-mediated membrane re-modelling of myeloid cells as a novel feature of these granulomas. Our study provides new insights into local immunometabolic changes associated with granuloma formation and macrophage activation.