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- Title
Reprogramming Neutral Lipid Metabolism in Mouse Dendritic Leucocytes Hosting Live Leishmania amazonensis Amastigotes.
- Authors
Lecoeur, Hervé; Giraud, Emilie; Prévost, Marie-Christine; Milon, Geneviève; Lang, Thierry
- Abstract
Background: 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. Methodology/Principal Findings: 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. Conclusions/Significance: 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? Author Summary: Once they have gained entry to mammals, live Leishmania (L) amazonensis amastigotes are known to subvert both macrophages and dendritic leucocytes (DLs) as host cells. These L. amazonensis amastigotes then may or may not proliferate in these two phagocytic leucocyte lineages, but in both cases the otherwise versatile differentiation program of these lineages is known to be rapidly remodeled. Here, we describe the rapid reprogramming of C57BL/6 and DBA/2 mouse bone marrow-derived DLs, with a special focus on cytosolic lipid bodies (LBs) that are known to store neutral lipids such as triacyl-sn-glycerol (TAG) and cholesteryl esters (CE). After extracting RNA from carefully sorted amastigote-free DLs and L. amazonensis amastigote-hosting DLs, an Affymetrix-based analysis clearly showed a singular and coordinated increase in DL transcripts involved in (i) long-chain fatty acid uptake, transport and esterification to TAG and (ii) cholesterol uptake and esterification to cholesteryl esters. Oleic acid was added to check that neutral lipid metabolism was both rapidly increased and reprogrammed in amastigote-hosting DLs. It should be noted that the LBs in live amastigote-hosting DLs were more numerous, and that the largest of these LBs were in contact with live amastigote- hosting parasitophorous vacuoles. We further discuss these findings in the context of live L. amazonensis amastigote-rodent host interactions.
- Subjects
LIPID metabolism; AMASTIGOTES; LEUCOCYTES; CHOLESTEROL content of food; OLEIC acid; TRANSMISSION electron microscopy; EPICATECHIN
- Publication
PLoS Neglected Tropical Diseases, 2013, Vol 7, Issue 6, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0002276