Defensive lipid droplets are PUFA reservoirs driving bacterial clearance and inflammation

Bosch, M.; Parida, G. L.; Sanchez-Quijada, M.; Ruiz-Mirapeix, C.; Sanchez-Alvarez, M.; Pedro-Cos, L.; Fajardo, A.; Lo, H.; Alonso-Bivou, M.; Safi, R.; Pineda, E.; Rae, J.; Curson, J. E.; Keller, B.; Balsinde, J.; Planas, A. M.; Sweet, M. J.; Herms, A.; Demangel, C.; Parton, R. G.; Pol, A.

doi:10.64898/2026.03.12.711356

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bioRxiv · 10.64898/2026.03.12.711356

Defensive lipid droplets are PUFA reservoirs driving bacterial clearance and inflammation

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Abstract

Lipid droplets (LDs) rapidly form in infected cells to participate in the defence against microbes. Here, we investigate the involvement of LD lipids in these immune responses. Comparative shotgun and targeted lipidomics demonstrate that in vivo host LDs accumulate polyunsaturated fatty acids (PUFAs). PUFAs arrive at cells from the bloodstream to be further metabolised into complex PUFAs accrued by LD-triglycerides and -phospholipids. Host lipid metabolism is transcriptionally controlled by rapid, transient, and intricate immune programs initiated by pathogen-associated molecular patterns and relayed by cytokines such as interferons (type I and II), interleukins (IL-1{beta}), and tumour necrosis factor. When this lipid and signalling environment is reproduced in cultured macrophages, newly formed LDs accumulate defensive proteins, coordinate the synthesis of complex PUFAs, and become PUFA reservoirs and suppliers. Among LD-PUFAs, the {omega}-6 arachidonic acid is the most actively metabolised during the initial phases of innate immunity. Released from LDs by adipose triglyceride lipase, arachidonic acid is used by macrophages for prostaglandin synthesis, bacterial phagocytosis, and elimination of microbes. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=163 HEIGHT=200 SRC="FIGDIR/small/711356v2_ufig1.gif" ALT="Figure 1"> View larger version (107K): org.highwire.dtl.DTLVardef@14d65eorg.highwire.dtl.DTLVardef@5ecc1org.highwire.dtl.DTLVardef@fa99e5org.highwire.dtl.DTLVardef@8d9632_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Bosch, M., Parida, G. L., Sanchez-Quijada, M., Ruiz-Mirapeix, C., Sanchez-Alvarez, M., Pedro-Cos, L., Fajardo, A., Lo, H., Alonso-Bivou, M., Safi, R., Pineda, E., Rae, J., Curson, J. E., Keller, B., Balsinde, J., Planas, A. M., Sweet, M. J., Herms, A., Demangel, C., Parton, R. G., Pol, A.. 2026-03-13. Defensive lipid droplets are PUFA reservoirs driving bacterial clearance and inflammation. https://doi.org/10.64898/2026.03.12.711356

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