Malaria Parasites Hijack Host Receptors From Exosomes to Capture Lipoproteins

Iso-O, Naoyuki; Komatsuya, Keisuke; Tokumasu, Fuyuki; Isoo, Noriko; Ishigaki, Tomohiro; Yotsuyanagi, Hiroshi; Hara, Mariko; Kita, Kiyoshi

doi:10.3389/fcell.2021.749153

Cited by 4 publications

(6 citation statements)

References 43 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Data from the malaria literature suggest that decreases in HDL associated with babesiosis may be directly related to the growth of the parasite. Multiple studies have shown that Plasmodium spp., Apicomplexans protozoa that are closely related to Babesia spp., does not possess the biosynthetic pathway for de novo synthesis of cholesterol and must scavenge this important molecule from host hepatocyte and erythrocyte membranes [22][23][24]. In humans, acute malaria infections are associated with lower LDL and HDL and the total cholesterol [25].…”

Section: Discussionmentioning

confidence: 99%

Reduced Cholesterol Levels during Acute Human Babesiosis

et al. 2023

View full text Add to dashboard Cite

Background: Babesiosis, an intra-erythrocytic protozoan disease, is an emerging zoonotic parasitic disease worldwide. Cholesterol levels are correlated with severe infections, such as sepsis and COVID-19, and anecdotal reports suggest that high-density lipoprotein (HDL) cholesterol declines during acute babesiosis. Our aim was to describe the cholesterol levels in patients with acute babesiosis diagnosed in an endemic area in New York, hypothesizing that HDL levels correlate with the severity of infection. Methods: We reviewed the medical records of adult patients with babesiosis diagnosed by identification of Babesia parasites on a thin blood smear and confirmed by polymerase chain reaction from 2013 to 2018, who also had available a lipid profile drawn at the time of clinical presentation. Additional lipid profile levels were considered as “baseline” if they were drawn within 2 months before or after the infection as part of routine care. Results: A total of 39 patients with babesiosis had a lipid profile drawn on presentation. The patients were divided into two groups for comparison based on the treating physician’s clinical decision: 33 patients who were admitted to the hospital and 8 patients who were evaluated as outpatients. A history of hypertension was more common in admitted patients (37% vs. 17%, p = 0.02). The median levels of low-density lipoprotein (LDL) and HDL were significantly reduced in admitted patients compared to non-admitted patients (46 vs. 76 mg/dL, p = 0.04; and 9 vs. 28.5 mg/dL, p = 0.03, respectively). In addition, LDL and HDL levels returned to baseline values following resolution of acute babesiosis. Conclusion: LDL and HDL levels are significantly reduced during acute babesiosis, suggesting that cholesterol depletion may predict disease severity. Pathogen and host factors may contribute to a reduction in serum cholesterol levels during acute babesiosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Reduced Cholesterol Levels during Acute Human Babesiosis

et al. 2023

View full text Add to dashboard Cite

show abstract

“…DIC is associated with more severe disease and cerebral malaria, and as such, high mortality [ 206 ]. In malaria infection, both in people ( Plasmodium falciparum and vivax ) and in mice ( Plasmodium berghei ) there are higher numbers of circulating EVs and PEVs [ 70 , 71 , 207 ]. PEVs in malaria positively correlate with clinical symptoms, including fever, cerebral malaria, coma depth, thrombocytopenia, and length of symptoms [ 70 , 71 ].…”

Section: Platelet-derived Extracellular Vesicles In Infectious Diseasesmentioning

confidence: 99%

“…PEVs in malaria affect coagulation by interacting with and activating other cell types. First, PEVs can bind to and be taken up by parasitized red blood cells (pRBC) [ 145 , 207 ]. In doing so, the PEV transfers both cholesterol and platelet antigens to the surface of the pRBC.…”

Section: Platelet-derived Extracellular Vesicles In Infectious Diseasesmentioning

confidence: 99%

“…In doing so, the PEV transfers both cholesterol and platelet antigens to the surface of the pRBC. While the cholesterol serves as a necessary resource for pathogen replication [ 207 ], the platelet antigens facilitate cytoadherence to brain endothelial cells [ 145 ], promoting cerebral malaria. PEVs had minimal binding to uninfected RBC.…”

Section: Platelet-derived Extracellular Vesicles In Infectious Diseasesmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Platelet-Derived Extracellular Vesicles in Immune-Mediated Thrombosis

Eustes

Dayal

2022

IJMS

View full text Add to dashboard Cite

Platelet-derived extracellular vesicles (PEVs) play important roles in hemostasis and thrombosis. There are three major types of PEVs described based on their size and characteristics, but newer types may continue to emerge owing to the ongoing improvement in the methodologies and terms used to define various types of EVs. As the literature on EVs is growing, there are continuing attempts to standardize protocols for EV isolation and reach consensus in the field. This review provides information on mechanisms of PEV production, characteristics, cellular interaction, and their pathological role, especially in autoimmune and infectious diseases. We also highlight the mechanisms through which PEVs can activate parent cells in a feedback loop.

show abstract

“…Lipid synthesis throughout the life cycle of malaria parasites range from fatty acid synthesis to lipid droplet formation with neutral lipids 2,4 . Although most lipid classes can also be scavenged from the host cytoplasm and extracellular environment, parasites must maintain a stable balance of fatty acids and phospholipid and neutral lipid synthesis to meet the diverse needs of these molecules at different stages and environments 5–8 .…”

Section: Introductionmentioning

confidence: 99%

Pivotal roles ofPlasmodium falciparumlysophospholipid acyltransferase 1 in cell cycle progression and cytostome internalization

Fukumoto,

Yoshida,

Tokuoka

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

The rapid intraerythrocytic replication of Plasmodium falciparum, a deadly species of malaria parasite, requires a quick but constant supply of phospholipids to support marked cell membrane expansion. In the malarial parasite, many enzymes functioning in phospholipid synthesis pathway have not been identified or characterized. Here, we identified P. falciparum lysophospholipid acyltransferase 1 (PfLPLAT1; PF3D7_1444300) and showed that PfLPLAT1 is vital for asexual parasite cell cycle progression and cytostome internalization. Deficiency in PfLPLAT1 resulted in decreased parasitemia and prevented transition to the schizont stage. Parasites lacking PfLPLAT1 also exhibited distinctive omega-shaped vacuoles, indicating disrupted cytostome function. Transcriptomic analyses suggested that this deficiency impacted DNA replication and cell cycle regulation. Mass spectrometry-based enzyme assay and lipidomic analysis demonstrated that recombinant PfLPLAT1 exhibited lysophospholipid acyltransferase activity with a preference for unsaturated fatty acids as its acyl donors and lysophosphatidic acids as an acceptor, with its conditional knockout leading to abnormal lipid composition and marked morphological and developmental changes including stage arrest. These findings highlight PfLPLAT1 as a potential target for antimalarial therapy, particularly due to its unique role and divergence from human orthologs.

show abstract

Malaria Parasites Hijack Host Receptors From Exosomes to Capture Lipoproteins

Cited by 4 publications

References 43 publications

Reduced Cholesterol Levels during Acute Human Babesiosis

Reduced Cholesterol Levels during Acute Human Babesiosis

The Role of Platelet-Derived Extracellular Vesicles in Immune-Mediated Thrombosis

Pivotal roles ofPlasmodium falciparumlysophospholipid acyltransferase 1 in cell cycle progression and cytostome internalization

Contact Info

Product

Resources

About