Culture of mouse peritoneal macrophages with mouse serum induces lipid bodies that associate with the parasitophorous vacuole and decrease their microbicidal capacity against Toxoplasma gondii

Mota, Laura Azeredo Miranda; Neto, João Roberto; Monteiro, V.G; Lobato, Caroliny Samary Silva; Oliveira, Marco Antônio de; Cunha, Maura Da; D’Avila, Heloísa; Seabra, Sérgio Henrique; Bozza, Patrı́cia T.; DaMatta, Renato Augusto

doi:10.1590/0074-0276140119

Cited by 20 publications

(29 citation statements)

References 34 publications

(48 reference statements)

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“…[25, 26]. To determine if a similar effect occurs in other cell types, human fibroblasts (HFF) and epithelial cells (HeLa) were infected in vitro with Toxoplasma , and LD biogenesis was monitored throughout infection.…”

Section: Resultsmentioning

confidence: 99%

Host lipid droplets: An important source of lipids salvaged by the intracellular parasite Toxoplasma gondii

2017

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Toxoplasma is an obligate intracellular parasite that replicates in mammalian cells within a parasitophorous vacuole (PV) that does not fuse with any host organelles. One mechanism developed by the parasite for nutrient acquisition is the attraction of host organelles to the PV. Here, we examined the exploitation of host lipid droplets (LD), ubiquitous fat storage organelles, by Toxoplasma. We show that Toxoplasma replication is reduced in host cells that are depleted of LD, or impaired in TAG lipolysis or fatty acid catabolism. In infected cells, the number of host LD and the expression of host LD-associated genes (ADRP, DGAT2), progressively increase until the onset of parasite replication. Throughout infection, the PV are surrounded by host LD. Toxoplasma is capable of accessing lipids stored in host LD and incorporates these lipids into its own membranes and LD. Exogenous addition of oleic acid stimulates LD biogenesis in the host cell and results in the overaccumulation of neutral lipids in very large LD inside the parasite. To access LD-derived lipids, Toxoplasma intercepts and internalizes within the PV host LD, some of which remaining associated with Rab7, which become wrapped by an intravacuolar network of membranes (IVN). Mutant parasites impaired in IVN formation display diminished capacity of lipid uptake from host LD. Moreover, parasites lacking an IVN-localized phospholipase A2 are less proficient in salvaging lipids from host LD in the PV, suggesting a major contribution of the IVN for host LD processing in the PV and, thus lipid content release. Interestingly, gavage of parasites with lipids unveils, for the first time, the presence in Toxoplasma of endocytic-like structures containing lipidic material originating from the PV lumen. This study highlights the reliance of Toxoplasma on host LD for its intracellular development and the parasite’s capability in scavenging neutral lipids from host LD.

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Section: Resultsmentioning

confidence: 99%

Host lipid droplets: An important source of lipids salvaged by the intracellular parasite Toxoplasma gondii

2017

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“…The peritoneal cells, mainly macrophages and lymphocytes that could provide the cell factor for clone formation, were rapidly depleted within 1 week under culture conditions, because they could not proliferate in vitro without the specific factors. 44,45 To exclude liver fibroblast contamination, the main cell markers of liver fibroblasts (CD34, CD90, AFP, and ALB) for cells isolated with the CSP and MACS methods were investigated by flow cytometry. The results showed that they all expressed below 5% (Fig.…”

Section: Isolation and Characterization Of Hflscsmentioning

confidence: 99%

A Convenient and Efficient Method to Enrich and Maintain Highly Proliferative Human Fetal Liver Stem Cells

Guo

Wang

Dou

et al. 2015

Rejuvenation Research

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Pluripotent human hepatic stem cells have broad research and clinical applications, which are, however, restricted by both limited resources and technical difficulties with respect to isolation of stem cells from the adult or fetal liver. In this study, we developed a convenient and efficient method involving a two-step in situ collagenase perfusion, gravity sedimentation, and Percoll density gradient centrifugation to enrich and maintain highly proliferative human fetal liver stem cells (hFLSCs). Using this method, the isolated hFLSCs entered into the exponential growth phase within 10 days and maintained sufficient proliferative activity to permit subculture for at least 20 passages without differentiation. Immunocytochemistry, immunofluorescence, and flow cytometry results showed that these cells expressed stem cell markers, such as c-kit, CD44, epithelial cell adhesion molecule (EpCAM), oval cell marker-6 (OV-6), epithelial marker cytokeratin 18 (CK18), biliary ductal marker CK19, and alpha-fetoprotein (AFP). Gene expression analysis showed that these cells had stable mRNA expression of c-Kit, EpCAM, neural cell adhesion molecule (NCAM), CK19, CK18, AFP, and claudin 3 (CLDN-3) throughout each passage while maintaining low levels of ALB, but with complete absence of cytochrome P450 3A4 (C3A4), phosphoenolpyruvate carboxykinase (PEPCK), telomeric repeat binding factor (TRF), and connexin 26 (CX26) expression. When grown in appropriate medium, these isolated liver stem cells could differentiate into hepatocytes, cholangiocytes, osteoblasts, adipocytes, or endothelial cells. Thus, we have demonstrated a more economical and efficient method to isolate hFLSCs than magnetic-activated cell sorting (MACS). This novel approach may provide an excellent tool to isolate highly proliferative hFLSCs for tissue engineering and regenerative therapies.

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“…Furthermore, LDs are also involved in inflammatory and infectious diseases . The participation of LDs in infectious disease pathogenesis has been reported for all classes of pathogens, such as viruses, bacteria, fungi, and protozoa, suggesting that LDs participate in the innate and adaptative host immune response to infection. Host LDs may also be exploit as part of the adaptation of pathogens to escape the immune system and as an energy source for intracellular pathogens .…”

Section: Introductionmentioning

confidence: 99%

“…21,22 Furthermore, LDs are also involved in inflammatory and infectious diseases. 23 The participation of LDs in infectious disease pathogenesis has been reported for all classes of pathogens, such as viruses, 24,25 bacteria, 26,27 fungi, 28 and protozoa, 29,30 suggesting that…”

mentioning

confidence: 99%

Fat, fight, and beyond: The multiple roles of lipid droplets in infections and inflammation

Pereira-Dutra

Teixeira

Costa

et al. 2019

Journal of Leukocyte Biology

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Increased accumulation of cytoplasmic lipid droplets (LDs) in host nonadipose cells is commonly observed in response to numerous infectious diseases, including bacterial, parasite, and fungal infections. LDs are lipid‐enriched, dynamic organelles composed of a core of neutral lipids surrounded by a monolayer of phospholipids associated with a diverse array of proteins that are cell and stimulus regulated. Far beyond being simply a deposit of neutral lipids, LDs have come to be seen as an essential platform for various cellular processes, including metabolic regulation, cell signaling, and the immune response. LD participation in the immune response occurs as sites for compartmentalization of several immunometabolic signaling pathways, production of inflammatory lipid mediators, and regulation of antigen presentation. Infection‐driven LD biogenesis is a complexly regulated process that involves innate immune receptors, transcriptional and posttranscriptional regulation, increased lipid uptake, and new lipid synthesis. Accumulating evidence demonstrates that intracellular pathogens are able to exploit LDs as an energy source, a replication site, and/or a mechanism of immune response evasion. Nevertheless, LDs can also act in favor of the host as part of the immune and inflammatory response to pathogens. Here, we review recent findings that explored the new roles of LDs in the context of host‐pathogen interactions.

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Culture of mouse peritoneal macrophages with mouse serum induces lipid bodies that associate with the parasitophorous vacuole and decrease their microbicidal capacity against Toxoplasma gondii

Cited by 20 publications

References 34 publications

Host lipid droplets: An important source of lipids salvaged by the intracellular parasite Toxoplasma gondii

Host lipid droplets: An important source of lipids salvaged by the intracellular parasite Toxoplasma gondii

A Convenient and Efficient Method to Enrich and Maintain Highly Proliferative Human Fetal Liver Stem Cells

Fat, fight, and beyond: The multiple roles of lipid droplets in infections and inflammation

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