Sickle Cell Hemoglobin Genotypes Affect Malaria Parasite Growth and Correlate with Exosomal miR-451a and let-7i-5p Levels

Harp, Keri Oxendine; Bashi, Alaijah; Botchway, Felix; Addo-Gyan, Daniel; Tetteh-Tsifoanya, Mark; Lamptey, Amanda N. L.; Djameh, Georgina Isabella; Iqbal, Shareen; Lekpor, Cecilia; Banerjee, Saswati; Wilson, Michael D.; Dei‐Adomakoh, Yvonne; Adjei, Andrew A.; Stiles, Jonathan K.; Driss, Adel

doi:10.3390/ijms24087546

Cited by 3 publications

(1 citation statement)

References 45 publications

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“…These EVs contain parasite‐specific bioactive substances including proteins, RNA, lncRNA and nucleic acids. In human protozoan parasitic diseases such as malaria, African sleeping sickness, Chagas disease, leishmaniasis and toxoplasmosis, EVs serve as a carrier of effector molecules that modulate the host immune response to establish infection (da Silva Lira Filho et al., 2021 ; Dias‐Guerreiro et al, 2021 ; Higuchi et al, 2018 ; Li, Xiu, et al, 2018 ; Oxendine Harp et al, 2023 ). It was reported that Leishmania EVs can transfer Leishmania RNA virus 1 (LRV1), a virus that infects Leishmania and enhances its virulence, to macrophages and induce type‐I interferon responses (Atayde et al., 2019 ).…”

Section: Roles Of Evs In the Pathogenesis Of Infectious Diseasesmentioning

confidence: 99%

Extracellular vesicles and endothelial dysfunction in infectious diseases

Zhang,

Chi,

et al. 2024

J of Extracellular Bio

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Cardiovascular diseases (CVDs) remain the leading cause of mortality and morbidity globally. Studies have shown that infections especially bacteraemia and sepsis are associated with increased risks for endothelial dysfunction and related CVDs including atherosclerosis. Extracellular vesicles (EVs) are small, sealed membrane‐derived structures that are released into body fluids and blood from cells and/or microbes and are critically involved in a variety of important cell functions and disease development, including intercellular communications, immune responses and inflammation. It is known that EVs‐mediated mechanism(s) is important in the development of endothelial dysfunction in infections with a diverse spectrum of microorganisms including Escherichia coli, Candida albicans, SARS‐CoV‐2 (the virus for COVID‐19) and Helicobacter pylori. H. pylori infection is one of the most common infections globally. During H. pylori infection, EVs can carry H. pylori components, such as lipopolysaccharide, cytotoxin‐associated gene A, or vacuolating cytotoxin A, and transfer these substances into endothelial cells, triggering inflammatory responses and endothelial dysfunction. This review is to illustrate the important role of EVs in the pathogenesis of infectious diseases, and the development of endothelial dysfunction in infectious diseases especially H. pylori infection, and to discuss the potential mechanisms and clinical implications.

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Section: Roles Of Evs In the Pathogenesis Of Infectious Diseasesmentioning

confidence: 99%

Extracellular vesicles and endothelial dysfunction in infectious diseases

Zhang,

Chi,

et al. 2024

J of Extracellular Bio

View full text Add to dashboard Cite

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Advances in personalized epigenetics in infectious diseases

Arumugam,

Dayaram,

Gokul

et al. 2024

Personalized Epigenetics

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Modulation of Heme-Induced Inflammation Using MicroRNA-Loaded Liposomes: Implications for Hemolytic Disorders Such as Malaria and Sickle Cell Disease

Bashi,

Lekpor,

Hood

et al. 2023

IJMS

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Hemolytic disorders, like malaria and sickle cell disease (SCD), are responsible for significant mortality and morbidity rates globally, specifically in the Americas and Africa. In both malaria and SCD, red blood cell hemolysis leads to the release of a cytotoxic heme that triggers the expression of unique inflammatory profiles, which mediate the tissue damage and pathogenesis of both diseases. MicroRNAs (miRNAs), such as miR-451a and let-7i-5p, contribute to a reduction in the pro-inflammatory responses induced by circulating free hemes. MiR-451a targets both IL-6R (pro-inflammatory) and 14-3-3ζ (anti-inflammatory), and when this miRNA is present, IL-6R is reduced and 14-3-3ζ is increased. Let-7i-5p targets and reduces TLR4, which results in anti-inflammatory signaling. These gene targets regulate inflammation via NFκB regulation and increase anti-inflammatory signaling. Additionally, they indirectly regulate the expression of key heme scavengers, such as heme-oxygenase 1 (HO-1) (coded by the HMOX1 gene) and hemopexin, to decrease circulating cytotoxic heme concentration. MiRNAs can be transported within extracellular vesicles (EVs), such as exosomes, offering insights into the mechanisms of mitigating heme-induced inflammation. We tested the hypothesis that miR-451a- or let-7i-5p-loaded artificial EVs (liposomes) will reduce heme-induced inflammation in brain vascular endothelial cells (HBEC-5i, ATCC: CRL-3245) and macrophages (THP-1, ATCC: TIB-202) in vitro. We completed arginase and nitric oxide assays to determine anti- and pro-inflammatory macrophage presence, respectively. We also assessed the gene expression of IL-6R, TLR4, 14-3-3ζ, and NFκB by RT-qPCR for both cell lines. Our findings revealed that the exposure of HBEC-5i and THP-1 to liposomes loaded with miR-451a or let-7i-5p led to a reduced mRNA expression of IL-6R, TLR4, 14-3-3ζ, and NFκB when treated with a heme. It also resulted in the increased expression of HMOX1 and hemopexin. Finally, macrophages exhibited a tendency toward adopting an anti-inflammatory differentiation phenotype. These findings suggest that miRNA-loaded liposomes can modulate heme-induced inflammation and can be used to target specific cellular pathways, mediating inflammation common to hematological conditions, like malaria and SCD.

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Sickle Cell Hemoglobin Genotypes Affect Malaria Parasite Growth and Correlate with Exosomal miR-451a and let-7i-5p Levels

Cited by 3 publications

References 45 publications

Extracellular vesicles and endothelial dysfunction in infectious diseases

Extracellular vesicles and endothelial dysfunction in infectious diseases

Advances in personalized epigenetics in infectious diseases

Modulation of Heme-Induced Inflammation Using MicroRNA-Loaded Liposomes: Implications for Hemolytic Disorders Such as Malaria and Sickle Cell Disease

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