Reprogramming neutral lipid metabolism in mouse dendritic leucocytes hosting live Leishmania amazonensis amastigotes
After loading with live Leishmania (L) amazonensis amastigotes, mouse myeloid dendritic leucocytes/DLs are known to undergo reprogramming of their immune functions. In the study reported here, we investigated whether the presence of live L. amazonensis amastigotes in mouse bone marrow-derived DLs is...
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| creator | Lecoeur, Hervé Giraud, Emilie Prévost, Marie-Christine Milon, Geneviève Lang, Thierry |
| description | After loading with live Leishmania (L) amazonensis amastigotes, mouse myeloid dendritic leucocytes/DLs are known to undergo reprogramming of their immune functions. In the study reported here, we investigated whether the presence of live L. amazonensis amastigotes in mouse bone marrow-derived DLs is able to trigger re-programming of DL lipid, and particularly neutral lipid metabolism.
Affymetrix-based transcriptional profiles were determined in C57BL/6 and DBA/2 mouse bone marrow-derived DLs that had been sorted from cultures exposed or not to live L. amazonensis amastigotes. This showed that live amastigote-hosting DLs exhibited a coordinated increase in: (i) long-chain fatty acids (LCFA) and cholesterol uptake/transport, (ii) LCFA and cholesterol (re)-esterification to triacyl-sn-glycerol (TAG) and cholesteryl esters (CE), respectively. As these neutral lipids are known to make up the lipid body (LB) core, oleic acid was added to DL cultures and LB accumulation was compared in live amastigote-hosting versus amastigote-free DLs by epi-fluorescence and transmission electron microscopy. This showed that LBs were both significantly larger and more numerous in live amastigote-hosting mouse dendritic leucocytes. Moreover, many of the larger LB showed intimate contact with the membrane of the parasitophorous vacuoles hosting the live L. amazonensis amastigotes.
As leucocyte LBs are known to be more than simple neutral lipid repositories, we set about addressing two related questions. Could LBs provide lipids to live amastigotes hosted within the DL parasitophorous vacuole and also deliver? Could LBs impact either directly or indirectly on the persistence of L. amazonensis amastigotes in rodent skin? |
| doi_str_mv | 10.1371/journal.pntd.0002276 |
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Affymetrix-based transcriptional profiles were determined in C57BL/6 and DBA/2 mouse bone marrow-derived DLs that had been sorted from cultures exposed or not to live L. amazonensis amastigotes. This showed that live amastigote-hosting DLs exhibited a coordinated increase in: (i) long-chain fatty acids (LCFA) and cholesterol uptake/transport, (ii) LCFA and cholesterol (re)-esterification to triacyl-sn-glycerol (TAG) and cholesteryl esters (CE), respectively. As these neutral lipids are known to make up the lipid body (LB) core, oleic acid was added to DL cultures and LB accumulation was compared in live amastigote-hosting versus amastigote-free DLs by epi-fluorescence and transmission electron microscopy. This showed that LBs were both significantly larger and more numerous in live amastigote-hosting mouse dendritic leucocytes. Moreover, many of the larger LB showed intimate contact with the membrane of the parasitophorous vacuoles hosting the live L. amazonensis amastigotes.
As leucocyte LBs are known to be more than simple neutral lipid repositories, we set about addressing two related questions. Could LBs provide lipids to live amastigotes hosted within the DL parasitophorous vacuole and also deliver? Could LBs impact either directly or indirectly on the persistence of L. amazonensis amastigotes in rodent skin?</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0002276</identifier><identifier>PMID: 23785538</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Biology ; Dendritic cells ; Dendritic Cells - metabolism ; Dendritic Cells - parasitology ; Development and progression ; Fatty acids ; Female ; Gene Expression Profiling ; Genetic aspects ; Genetic transcription ; Host-Pathogen Interactions ; Leishmania mexicana - immunology ; Leishmania mexicana - physiology ; Leishmaniasis ; Leucocytes ; Leukocytes ; Lipid Metabolism ; Lipids ; Metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA</subject><ispartof>PLoS neglected tropical diseases, 2013-06, Vol.7 (6), p.e2276-e2276</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Lecoeur et al 2013 Lecoeur et al</rights><rights>2013 Lecoeur et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Lecoeur H, Giraud E, Prévost M-C, Milon G, Lang T (2013) Reprogramming Neutral Lipid Metabolism in Mouse Dendritic Leucocytes Hosting Live Leishmania amazonensis Amastigotes. PLoS Negl Trop Dis 7(6): e2276. doi:10.1371/journal.pntd.0002276</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c596t-1a81cd65785344cff4e0e4f6be27fb9d0ecc549eb8f0395df934f35f02d02ac63</citedby><cites>FETCH-LOGICAL-c596t-1a81cd65785344cff4e0e4f6be27fb9d0ecc549eb8f0395df934f35f02d02ac63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681733/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681733/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23785538$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lecoeur, Hervé</creatorcontrib><creatorcontrib>Giraud, Emilie</creatorcontrib><creatorcontrib>Prévost, Marie-Christine</creatorcontrib><creatorcontrib>Milon, Geneviève</creatorcontrib><creatorcontrib>Lang, Thierry</creatorcontrib><title>Reprogramming neutral lipid metabolism in mouse dendritic leucocytes hosting live Leishmania amazonensis amastigotes</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>After loading with live Leishmania (L) amazonensis amastigotes, mouse myeloid dendritic leucocytes/DLs are known to undergo reprogramming of their immune functions. In the study reported here, we investigated whether the presence of live L. amazonensis amastigotes in mouse bone marrow-derived DLs is able to trigger re-programming of DL lipid, and particularly neutral lipid metabolism.
Affymetrix-based transcriptional profiles were determined in C57BL/6 and DBA/2 mouse bone marrow-derived DLs that had been sorted from cultures exposed or not to live L. amazonensis amastigotes. This showed that live amastigote-hosting DLs exhibited a coordinated increase in: (i) long-chain fatty acids (LCFA) and cholesterol uptake/transport, (ii) LCFA and cholesterol (re)-esterification to triacyl-sn-glycerol (TAG) and cholesteryl esters (CE), respectively. As these neutral lipids are known to make up the lipid body (LB) core, oleic acid was added to DL cultures and LB accumulation was compared in live amastigote-hosting versus amastigote-free DLs by epi-fluorescence and transmission electron microscopy. This showed that LBs were both significantly larger and more numerous in live amastigote-hosting mouse dendritic leucocytes. Moreover, many of the larger LB showed intimate contact with the membrane of the parasitophorous vacuoles hosting the live L. amazonensis amastigotes.
As leucocyte LBs are known to be more than simple neutral lipid repositories, we set about addressing two related questions. Could LBs provide lipids to live amastigotes hosted within the DL parasitophorous vacuole and also deliver? Could LBs impact either directly or indirectly on the persistence of L. amazonensis amastigotes in rodent skin?</description><subject>Animals</subject><subject>Biology</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - metabolism</subject><subject>Dendritic Cells - parasitology</subject><subject>Development and progression</subject><subject>Fatty acids</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Genetic aspects</subject><subject>Genetic transcription</subject><subject>Host-Pathogen Interactions</subject><subject>Leishmania mexicana - immunology</subject><subject>Leishmania mexicana - physiology</subject><subject>Leishmaniasis</subject><subject>Leucocytes</subject><subject>Leukocytes</subject><subject>Lipid Metabolism</subject><subject>Lipids</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred DBA</subject><issn>1935-2735</issn><issn>1935-2727</issn><issn>1935-2735</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNptkl2L1DAUhoso7rr6D0QLgngzY9I0bXojLIsfCwOC6HVIk5NOhnyMSbqw_npTZ3aZAclFQvK8b07enKp6jdEakx5_3IU5emHXe5_VGiHUNH33pLrEA6Grpif06cn6onqR0g4hOlCGn1cXDekZpYRdVvkH7GOYonDO-Kn2MOcobG3N3qjaQRZjsCa52vjahTlBrcCraLKRtYVZBnmfIdXbkPIit-YO6g2YtHXCG1ELJ_4EDz6ZtKwLNIXCv6yeaWETvDrOV9WvL59_3nxbbb5_vb253qwkHbq8woJhqTpaaiVtK7VuAUGruxGaXo-DQiAlbQcYmUZkoEoPpNWEatQo1AjZkavq7cF3b0Pix8ASx23JpMOoo4W4PRAqiB3fR-NEvOdBGP5vI8SJi1gea4GjQQvBdLmfkZYxEGpkFPVdo3sNDUHF69Pxtnl0oCT4Jcoz0_MTb7Z8CnecdAz3hBSDD0eDGH7PkDJ3JkmwVngo2fPy7agjFKGhoO8O6CRKacbrUBzlgvNrQvqGMTSwQq3_Q5WhwBlZPkabsn8meH8i2IKweZuCnbMJPp2D7QGUMaQUQT8-E6OlTvyQNl_akx_bs8jenEb0KHroR_IX33jlwA</recordid><startdate>20130601</startdate><enddate>20130601</enddate><creator>Lecoeur, Hervé</creator><creator>Giraud, Emilie</creator><creator>Prévost, Marie-Christine</creator><creator>Milon, Geneviève</creator><creator>Lang, Thierry</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130601</creationdate><title>Reprogramming neutral lipid metabolism in mouse dendritic leucocytes hosting live Leishmania amazonensis amastigotes</title><author>Lecoeur, Hervé ; Giraud, Emilie ; Prévost, Marie-Christine ; Milon, Geneviève ; Lang, Thierry</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c596t-1a81cd65785344cff4e0e4f6be27fb9d0ecc549eb8f0395df934f35f02d02ac63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Biology</topic><topic>Dendritic cells</topic><topic>Dendritic Cells - metabolism</topic><topic>Dendritic Cells - parasitology</topic><topic>Development and progression</topic><topic>Fatty acids</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Genetic aspects</topic><topic>Genetic transcription</topic><topic>Host-Pathogen Interactions</topic><topic>Leishmania mexicana - immunology</topic><topic>Leishmania mexicana - physiology</topic><topic>Leishmaniasis</topic><topic>Leucocytes</topic><topic>Leukocytes</topic><topic>Lipid Metabolism</topic><topic>Lipids</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred DBA</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lecoeur, Hervé</creatorcontrib><creatorcontrib>Giraud, Emilie</creatorcontrib><creatorcontrib>Prévost, Marie-Christine</creatorcontrib><creatorcontrib>Milon, Geneviève</creatorcontrib><creatorcontrib>Lang, Thierry</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS neglected tropical diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lecoeur, Hervé</au><au>Giraud, Emilie</au><au>Prévost, Marie-Christine</au><au>Milon, Geneviève</au><au>Lang, Thierry</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reprogramming neutral lipid metabolism in mouse dendritic leucocytes hosting live Leishmania amazonensis amastigotes</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2013-06-01</date><risdate>2013</risdate><volume>7</volume><issue>6</issue><spage>e2276</spage><epage>e2276</epage><pages>e2276-e2276</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>After loading with live Leishmania (L) amazonensis amastigotes, mouse myeloid dendritic leucocytes/DLs are known to undergo reprogramming of their immune functions. In the study reported here, we investigated whether the presence of live L. amazonensis amastigotes in mouse bone marrow-derived DLs is able to trigger re-programming of DL lipid, and particularly neutral lipid metabolism.
Affymetrix-based transcriptional profiles were determined in C57BL/6 and DBA/2 mouse bone marrow-derived DLs that had been sorted from cultures exposed or not to live L. amazonensis amastigotes. This showed that live amastigote-hosting DLs exhibited a coordinated increase in: (i) long-chain fatty acids (LCFA) and cholesterol uptake/transport, (ii) LCFA and cholesterol (re)-esterification to triacyl-sn-glycerol (TAG) and cholesteryl esters (CE), respectively. As these neutral lipids are known to make up the lipid body (LB) core, oleic acid was added to DL cultures and LB accumulation was compared in live amastigote-hosting versus amastigote-free DLs by epi-fluorescence and transmission electron microscopy. This showed that LBs were both significantly larger and more numerous in live amastigote-hosting mouse dendritic leucocytes. Moreover, many of the larger LB showed intimate contact with the membrane of the parasitophorous vacuoles hosting the live L. amazonensis amastigotes.
As leucocyte LBs are known to be more than simple neutral lipid repositories, we set about addressing two related questions. Could LBs provide lipids to live amastigotes hosted within the DL parasitophorous vacuole and also deliver? Could LBs impact either directly or indirectly on the persistence of L. amazonensis amastigotes in rodent skin?</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23785538</pmid><doi>10.1371/journal.pntd.0002276</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biology Dendritic cells Dendritic Cells - metabolism Dendritic Cells - parasitology Development and progression Fatty acids Female Gene Expression Profiling Genetic aspects Genetic transcription Host-Pathogen Interactions Leishmania mexicana - immunology Leishmania mexicana - physiology Leishmaniasis Leucocytes Leukocytes Lipid Metabolism Lipids Metabolism Mice Mice, Inbred C57BL Mice, Inbred DBA |
| title | Reprogramming neutral lipid metabolism in mouse dendritic leucocytes hosting live Leishmania amazonensis amastigotes |
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