Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense

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 lipopolysacchar...

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Detalles Bibliográficos
Autores: Bosch, Marta, Sánchez-Álvarez, Miguel, Fajardo, Alba, Kapetanovic, Ronan, Steiner, Bernhard, Dutra, Filipe, Moreira, Luciana, López, Juan Antonio, Campo, Rocío, Marí, Montserrat, Morales-Paytuvi, Frederic, Tort, Olivia, Gubern, Albert, Templin, Rachel M., Curson, James E. B., Martel, Nick, Catalá, Cristina, Lozano, Francisco, Tebar, Francesc, Enrich, Carlos, Vázquez, Jesús, Pozo Barriuso, Miguel Ángel del, Sweet, Matthew J., Bozza, Patricia T., Gross, Steven P., Parton, Robert G., Pol, Albert
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/224174
Acceso en línea:http://hdl.handle.net/10261/224174
Access Level:acceso abierto
Palabra clave:Lipid droplets
Mitochondria
Innate immunity
Immunometabolism
Proteomics
Antibiotics
Cathelicidins
Descripción
Sumario: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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