Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense
Open accessAbstract
Lipid droplets (LDs) are the major lipid storage organelles of eukaryotic cells and a source of nutrients for intracellular pathogens. We demonstrate that mammalian LDs are endowed with a protein-mediated antimicrobial capacity, which is up-regulated by danger signals. In response to lipopolysaccharide (LPS), multiple host defense proteins, including interferon-inducible guanosine triphosphatases and the antimicrobial cathelicidin, assemble into complex clusters on LDs. LPS additionally promotes the physical and functional uncoupling of LDs from mitochondria, reducing fatty acid metabolism while increasing LD-bacterial contacts. Thus, LDs actively participate in mammalian innate immunity at two levels: They are both cell-autonomous organelles that organize and use immune proteins to kill intracellular pathogens as well as central players in the local and systemic metabolic adaptation to infection.
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Lipid droplets have antimicrobial properties and are an evolutionarily conserved form of innate immune defence in macrophages.
“LDs themselves have antimicrobial properties and are an evolutionarily conserved form of innate immune defence in macrophages8.”
From APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia (2024) · cites this paper as [8]
CAMP is found on lipid droplet surfaces with antimicrobial properties in macrophages exposed to bacteria.
“which is found on LD surfaces with antimicrobial properties in macrophages exposed to bacteria8.”
From APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia (2024) · cites this paper as [8]
Innate immune triggers (e.g., Escherichia coli and Salmonella) induce lipid droplet formation in peripheral macrophages as part of an evolutionarily conserved antimicrobial defence in which LDs coated with antimicrobial proteins such as cathelicidin (CAMP) kill bacteria.
“A recent report showed that innate immune triggers (for example, Escherichia coli and Salmonella) induce LD formation in peripheral macrophages as part of an evolutionarily conserved antimicrobial defence in which LDs coated with antimicrobial proteins, such as cathelicidin (CAMP), kill bacteria8.”
From APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia (2024) · cites this paper as [8]
The innate immune protein cathelicidin reroutes to lipid droplets in response to OA loading or lipopolysaccharide treatment, retaining its N-terminal signal peptide.
“One study demonstrated that the innate immune protein cathelicidin reroutes to LDs in response to OA loading or lipopolysaccharide treatment, retaining its N-terminal signal peptide (Bosch et al., 2020).”
From APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size (2024) · cites this paper as Bosch et al., 2020
Both cell type and cellular environment modulate the lipid droplet proteome and lipidome.
“Importantly, both cell type and cellular environment modulate the lipid droplet proteome and lipidome3–9.”
From APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics (2026) · cites this paper as [4]
This finding mirrors observations in other systems where lipid droplets regulate immune responses.
“This finding mirrors observations in other systems where lipid droplets regulate immune responses4,70.”
From APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics (2026) · cites this paper as [4]
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Fiji: an open-source platform for biological-image analysis
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APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia
Haney, M. S., Pálovics, R., Munson, C. N., Long, C., Johansson, P. K., Yip, O., Dong, W., Rawat, E., West, E., Schlachetzki, J. C. M., et al. (2024) · Nature · doi:10.1038/s41586-024-07185-7 · Cited by 536 · see citing works
“LDs themselves have anti-microbial properties and are an evolutionarily conserved form of innate immune defence in macrophages 8 .”
InfluentialLipid droplets in the nervous system
Ralhan, I., Chang, C.-L., Lippincott-Schwartz, J., & Ioannou, M. S. (2021) · Journal of Cell Biology · doi:10.1083/jcb.202102136 · Cited by 281 · see citing works
The cell biology of APOE in the brain
Windham, I. A., & Cohen, S. (2024) · Trends in Cell Biology · doi:10.1016/j.tcb.2023.09.004 · Cited by 103 · see citing works
APOE traffics to astrocyte lipid droplets and modulates triglyceride saturation and droplet size
Windham, I. A., Powers, A. E., Ragusa, J. V., Wallace, E. D., Zanellati, M. C., Williams, V. H., Wagner, C. H., White, K. K., & Cohen, S. (2024) · Journal of Cell Biology · doi:10.1083/jcb.202305003 · Cited by 96 · see citing works
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Self-citationAPOE4 reshapes the lipid droplet proteome and modulates microglial inflammatory responses
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- Authors
- Bosch, M., Sánchez-Álvarez, M., Fajardo, A., Kapetanovic, R., Steiner, B., Dutra, F., Moreira, L., López, J. A., Campo, R., Marí, M., Morales-Paytuví, F., Tort, O., Gubern, A., Templin, R. M., Curson, J. E. B., Martel, N., Català, C., Lozano, F., Tebar, F., Enrich, C., Vázquez, J., Del Pozo, M. A., Sweet, M. J., Bozza, P. T., Gross, S. P., Parton, R. G., & Pol, A.
- Affiliations
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Mechanoadaptation and Caveolae Biology Laboratory, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC). 28029, Madrid, Spain.
- Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, Queensland 4072, Australia.
- The University of Queensland (AU)
- Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, CEP 21.040-900, Brazil.
- Instituto de Salud Carlos III (ES)
- Department of Cell Death and Proliferation, Institut d'Investigacions Biomèdiques de Barcelona (IIBB)–CSIC, Barcelona, Spain.
- University of California, Irvine (US)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Corresponding author
- Bosch, Marta
- Parton, Robert G.
- Pol, Albert
- ORCID
- Bosch, Marta
- Sánchez-Álvarez, Miguel
- Fajardo, Alba
- Kapetanovic, Ronan
- Dutra, Filipe
- Moreira, Luciana
- López, Juan Antonio
- Campo, Rocío
- Marí, Montserrat
- Morales-Paytuví, Frederic
- Tort, Olivia
- Gubern, Albert
- Templin, Rachel M.
- Curson, James E. B.
- Martel, Nick
- Català, Cristina
- Lozano, Francisco
- Tebar, Francesc
- Enrich, Carlos
- Vázquez, Jesús
- Del Pozo, Miguel A.
- Sweet, Matthew J.
- Bozza, Patricia T.
- Gross, Steven P.
- Parton, Robert G.
- Pol, Albert
- Venue
- Science
- Published
- 2020-10-16
- Volume
- 370
- Issue
- 6514
- Pages
- eaay8085
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W3093010709
- Cited by
- 480
- References
- 1
- Citations by year
- 2026: 69 · 2025: 89 · 2024: 86 · 2023: 73 · 2022: 82 · 2021: 72 · 2020: 7
- FWCI
- 24.87
- Type
- journal article
- Language
- en
- Open access
- green
- hal.inrae.fr
- Licence
- cc-by
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- Arca - Repositório Institucional da Fiocruz (submittedVersion, other-oa)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, public-domain)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- National Science Foundation
- Amgen
- Centres de Recerca de Catalunya
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (184024, 107914)
- University of Queensland
- Generalitat de Catalunya (PI19/01410)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
- Ministerio de Ciencia e Innovación (SEV-2015-0505, B-I00, BIO2015‐67580‐P, RTI2018-098593-B-I00)
- Universitat de Barcelona
- Centro Nacional de Investigaciones Cardiovasculares (SEV‐2015‐0505)
- Medical Research Council
- Australian Research Council (DE130100470)
- National Health and Medical Research Council (1037320, CE140100036, 569452, 1107914)
- Instituto de Salud Carlos III (SEV-2015-0505, BIO2015-67580-P, PI19/01410)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Keywords
- lipid droplets, innate immunity, antimicrobial activity, lipopolysaccharide, cathelicidin, mitochondrial uncoupling, fatty acid metabolism, intracellular pathogens, damage-associated molecular patterns, host defense proteins, lipid metabolism
- MeSH terms
- Animals, Bacteria, Fatty Acids, Humans, Immunity, Innate, Lipopolysaccharides, Macrophages, Male, Mice, Inbred C57BL, Mitochondria, GTP Phosphohydrolases, Antimicrobial Cationic Peptides, Mice, Cathelicidins, Host-Pathogen Interactions, HEK293 Cells, Lipid Droplets
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