1. Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense
- Author
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Albert Pol, Carlos Enrich, Olivia Tort, Matthew J. Sweet, Francesc Tebar, Nick Martel, James E. B. Curson, Steven P. Gross, Francisco Lozano, Patrícia T. Bozza, Filipe Dutra, Rachel Templin, Miguel A. del Pozo, Robert G. Parton, Juan Antonio López, Cristina Català, Frederic Morales-Paytuvi, Luciana Novaes Moreira, Montserrat Marí, Miguel Sánchez-Álvarez, Jesús Vázquez, Rocío Campo, Ronan Kapetanovic, Bernhard Steiner, Albert Gubern, Alba Fajardo, Marta Bosch, Fundación La Marató TV3, Australian Research Council, Swiss National Science Foundation, National Health and Medical Research Council (Australia), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Government of Catalonia (España), National Council for Scientific and Technological Development (Brasil), Worldwide Cancer Research, Fundación ProCNIC, Fundació La Marató, Instituto de Salud Carlos III - ISCIII, Generalitat de Catalunya, Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brazil), Fundació La Marató de TV3, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Ministerio de Economía y Competitividad (España), European Commission, and Centro Nacional de Investigaciones Cardiovasculares (España)
- Subjects
Proteomics ,0301 basic medicine ,Lipopolysaccharides ,Male ,Lipopolysaccharide ,medicine.medical_treatment ,Biology ,Cathelicidin ,GTP Phosphohydrolases ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Immune system ,Antibiotics ,Immunity ,Cathelicidins ,Lipid droplet ,Organelle ,medicine ,Animals ,Humans ,innate immunity ,Immunometabolism ,Multidisciplinary ,Innate immune system ,Bacteria ,Intracellular parasite ,Macrophages ,Fatty Acids ,Lipid Droplets ,Immunity, Innate ,Cell biology ,Mitochondria ,Mice, Inbred C57BL ,030104 developmental biology ,HEK293 Cells ,chemistry ,Host-Pathogen Interactions ,030217 neurology & neurosurgery ,Antimicrobial Cationic Peptides - Abstract
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., M.B. acknowledges support from 31/U/2016 from Fundació Marató de TV3. R.K. acknowledges support from an Australian Research Council Discovery Early Career Research Award (DE130100470). B.S. is supported by an Early Postdoc Mobility fellowship from the Swiss National Science Foundation (P2ZHP3_184024). M.J.S. is supported by a National Health and Medical Research Council (NHMRC) Senior Research Fellowship (APP1107914). M.S.-A. was recipient of a CNIC IPP fellowship (COFUND 2014). M.M. is supported by the Instituto de Salud Carlos III (FIS PI19/01410). O.T. is founded by Amgen 2018 Competitive Grant Program. A.P., R.G.P., S.P.G., and P.T.B. have been supported by RGP0020/2015 from the Human Frontier Science Program (HFSP). A.P. is supported by the Ministerio de Ciencia e Innovación (MICINN, RTI2018-098593-B-I00), Fundació Marató de TV3 (31/U/2016), and the CERCA Programme/Generalitat de Catalunya. R.G.P. was supported by the NHMRC of Australia (program grant APP1037320 and Senior Principal Research Fellowship 569452), and the Australian Research Council Centre of Excellence in Convergent Bio-Nanoscience and Technology (CE140100036). P.T.B. is supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) of Brazil and Fundaçao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ). M.A.D.P. was funded by MICINN (project grants SAF2014-51876-R and SAF2017-83130-R; and IGP-SO grant MINSEV1512-07-2016) and was a Worldwide Cancer Research Foundation grantee (#15-0404). J.V. is supported by MICINN (BIO2015-67580-P) and from the Carlos III Institute of Health-Fondo de Investigación Sanitaria (PRB2, IPT13/0001—ISCIII-SGEFI/FEDER, ProteoRed). The CNIC is supported by the MICINN and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MICINN award SEV-2015-0505).
- Published
- 2019