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Annals of Medicine Dec 2023Microscopy was used to characterize platelet--infected erythrocyte interactions in patients infected with , , or , and to investigate the relationship between...
OBJECTIVE
Microscopy was used to characterize platelet--infected erythrocyte interactions in patients infected with , , or , and to investigate the relationship between platelet-associated parasite killing and parasite clearance.
METHODS
Data from 244 malaria patients admitted to the Fourth People's Hospital of Nanning between 1 January 2011 and 30 September 2022, and 45 healthy controls, were collected prospectively and assessed retrospectively. Characteristics of platelet-erythrocyte interactions were visualized by microscopy, and blood cell count and clinical profiles of these participants were obtained from the electronic medical records. ANOVA, contingency tables and Cox proportional hazards regression models were used to do statistical analysis on the subgroups.
RESULTS
Platelet enlargement and minor pseudopodia development were observed. Platelets were found directly attaching to parasitized erythrocytes by all species studied, especially mature stages, and lysis of parasitized erythrocytes was connected to platelet-mediated cytolysis. Platelet counts were correlated inversely with parasitaemia and duration of parasite clearance. Artemisinin combination therapy was more effective than artemisinin alone in clearing in patients with thrombocytopenia.
CONCLUSIONS
Platelet-parasitized erythrocytes cell-to-cell contacts initiated platelet-associated parasite killing and helped to limit infection in cases of human malaria. The weakening platelet-associated parasite killing effects could be counteracted by artemisinin combination therapy in patients with thrombocytopenia.
Topics: Humans; Animals; Blood Platelets; Parasites; Retrospective Studies; Malaria; Thrombocytopenia; Artemisinins
PubMed: 37310126
DOI: 10.1080/07853890.2023.2221453 -
Frontiers in Immunology 2023Schistosomiasis is considered as a significant public health problem, imposing a deeper understanding of the intricate interplay between parasites and their hosts....
Schistosomiasis is considered as a significant public health problem, imposing a deeper understanding of the intricate interplay between parasites and their hosts. Unfortunately, current invasive methodologies employed to study the compatibility and the parasite development impose limitations on exploring diverse strains under various environmental conditions, thereby impeding progress in the field. In this study, we demonstrate the usefulness for the trematode parasite , leveranging a fluorescence-imaging-based approach that employs fluorescein 5-chloromethylfluorescein diacetate (CMFDA) and 5-chloromethylfluorescein diacetate (CMAC) as organism tracker for intramolluscan studies involving the host snail These probes represent key tools for qualitatively assessing snail infections with unmatched accuracy and precision. By monitoring the fluorescence of parasites within the snail vector, our method exposes an unprecedented glimpse into the host-parasite compatibility landscape. The simplicity and sensitivity of our approach render it an ideal choice for evolutionary studies, as it sheds light on the intricate mechanisms governing host-parasite interactions. Fluorescent probe-based methods play a pivotal role in characterizing factors influencing parasite development and phenotype of compatibility, paving the way for innovative, effective, and sustainable solutions to enhance our understanding host-parasite immunobiological interaction and compatibility.
Topics: Animals; Parasites; Schistosoma mansoni; Biomphalaria; Snails; Phenotype
PubMed: 38106408
DOI: 10.3389/fimmu.2023.1293009 -
Science Translational Medicine Dec 2023Chagas disease, caused by the protozoan parasite , affects millions of people in the Americas and across the world, leading to considerable morbidity and mortality....
Chagas disease, caused by the protozoan parasite , affects millions of people in the Americas and across the world, leading to considerable morbidity and mortality. Current treatment options, benznidazole (BNZ) and nifurtimox, offer limited efficacy and often lead to adverse side effects because of long treatment durations. Better treatment options are therefore urgently required. Here, we describe a pyrrolopyrimidine series, identified through phenotypic screening, that offers an opportunity to improve on current treatments. In vitro cell-based washout assays demonstrate that compounds in the series are incapable of killing all parasites; however, combining these pyrrolopyrimidines with a subefficacious dose of BNZ can clear all parasites in vitro after 5 days. These findings were replicated in a clinically predictive in vivo model of chronic Chagas disease, where 5 days of treatment with the combination was sufficient to prevent parasite relapse. Comprehensive mechanism of action studies, supported by ligand-structure modeling, show that compounds from this pyrrolopyrimidine series inhibit the Q active site of cytochrome b, part of the cytochrome bc complex of the electron transport chain. Knowledge of the molecular target enabled a cascade of assays to be assembled to evaluate selectivity over the human cytochrome b homolog. As a result, a highly selective and efficacious lead compound was identified. The combination of our lead compound with BNZ rapidly clears parasites, both in vitro and in vivo, and shows great potential to overcome key issues associated with currently available treatments.
Topics: Animals; Humans; Cytochromes b; Trypanocidal Agents; Chagas Disease; Trypanosoma cruzi; Parasites
PubMed: 38091410
DOI: 10.1126/scitranslmed.adg8105 -
Nature Communications Aug 2023The complex life cycle of Plasmodium falciparum requires coordinated gene expression regulation to allow host cell invasion, transmission, and immune evasion. Increasing...
The complex life cycle of Plasmodium falciparum requires coordinated gene expression regulation to allow host cell invasion, transmission, and immune evasion. Increasing evidence now suggests a major role for epigenetic mechanisms in gene expression in the parasite. In eukaryotes, many lncRNAs have been identified to be pivotal regulators of genome structure and gene expression. To investigate the regulatory roles of lncRNAs in P. falciparum we explore the intergenic lncRNA distribution in nuclear and cytoplasmic subcellular locations. Using nascent RNA expression profiles, we identify a total of 1768 lncRNAs, of which 718 (~41%) are novels in P. falciparum. The subcellular localization and stage-specific expression of several putative lncRNAs are validated using RNA-FISH. Additionally, the genome-wide occupancy of several candidate nuclear lncRNAs is explored using ChIRP. The results reveal that lncRNA occupancy sites are focal and sequence-specific with a particular enrichment for several parasite-specific gene families, including those involved in pathogenesis and sexual differentiation. Genomic and phenotypic analysis of one specific lncRNA demonstrate its importance in sexual differentiation and reproduction. Our findings bring a new level of insight into the role of lncRNAs in pathogenicity, gene regulation and sexual differentiation, opening new avenues for targeted therapeutic strategies against the deadly malaria parasite.
Topics: Humans; Animals; Plasmodium falciparum; RNA, Long Noncoding; Parasites; Malaria; Malaria, Falciparum
PubMed: 37607941
DOI: 10.1038/s41467-023-40883-w -
Indian Journal of Ophthalmology Sep 2023Ophthalmic dirofilariasis is an uncommon zoonotic parasitic infection caused by species of Dirofilaria, a dog tapeworm that is transmitted to human by mosquitoes. Man is...
BACKGROUND
Ophthalmic dirofilariasis is an uncommon zoonotic parasitic infection caused by species of Dirofilaria, a dog tapeworm that is transmitted to human by mosquitoes. Man is a dead-end host for the parasite. Ophthalmic involvement is rare and includes periorbital, subconjunctival, subtenon, and intra-ocular involvement. We report the removal of a subconjunctival worm and identification by light microscopy (LM) and scanning electron microscopy (SEM).
PURPOSE
: A 62-year-old female presented with complaints of redness, discharge, and foreign body sensation with difficulty in opening eyes in the left eye for the last 3 days. The patient is a non-vegetarian. On examination, her best corrected visual acuity in both eyes was 20/20. On slit lamp examination, there was a long, thin, round, coiled white subconjunctival live worm in the left eye superiorly. The rest of anterior segment evaluation, intra-ocular pressure, and fundus was normal in both eyes. The parasite was removed under local anesthesia from subconjunctival space [Video]. External surface morphology under LM revealed fine transverse cuticular striations with tapered cephalic and caudal ends. Uterus was long and coiled with indistinguishable masses inside. The finding was also confirmed by SEM.
SYNOPSIS
A subconjuctival parasite was removed and identified as Dirofilaria repens by characteristic LM and SEM findings.
HIGHLIGHT
Dirofilaria species may lodge in many tissues of human bodies including eye and adnexa. Dirofilaria is a natural parasite of carnivorous animals, mostly dogs, cats, and foxes. The most common mode of transmission to human is usually by bite of mosquitoes like Culex and Aedes, which are considered as vectors, and it is often thought that parasitemia is because of accidental conduction. Simple surgical removal of the worm is curative. After removal, the worm should be visualized directly under LM. All the internal structures of the transparent worm could be seen and compared with those under SEM.
Topics: Humans; Female; Male; Animals; Dogs; Middle Aged; Microscopy, Electron, Scanning; Parasites; Mosquito Vectors; Eye; Face
PubMed: 37602631
DOI: 10.4103/IJO.IJO_830_23 -
Proceedings. Biological Sciences Apr 2024The interplay of host-parasite and predator-prey interactions is critical in ecological dynamics because both predators and parasites can regulate communities. But what...
The interplay of host-parasite and predator-prey interactions is critical in ecological dynamics because both predators and parasites can regulate communities. But what is the prevalence of infected prey and predators when a parasite is transmitted through trophic interactions considering stochastic demographic changes? Here, we modelled and analysed a complex predator-prey-parasite system, where parasites are transmitted from prey to predators. We varied parasite virulence and infection probabilities to investigate how those evolutionary factors determine species' coexistence and populations' composition. Our results show that parasite species go extinct when the infection probabilities of either host are small and that success in infecting the final host is more critical for the survival of the parasite. While our stochastic simulations are consistent with deterministic predictions, stochasticity plays an important role in the border regions between coexistence and extinction. As expected, the proportion of infected individuals increases with the infection probabilities. Interestingly, the relative abundances of infected and uninfected individuals can have opposite orders in the intermediate and final host populations. This counterintuitive observation shows that the interplay of direct and indirect parasite effects is a common driver of the prevalence of infection in a complex system.
Topics: Animals; Host-Parasite Interactions; Food Chain; Predatory Behavior; Parasites; Models, Biological; Population Dynamics
PubMed: 38654648
DOI: 10.1098/rspb.2023.2468 -
Proceedings of the National Academy of... Aug 2023Long-lived parasites evade host immunity through highly evolved molecular strategies. The murine intestinal helminth, , down-modulates the host immune system through...
Long-lived parasites evade host immunity through highly evolved molecular strategies. The murine intestinal helminth, , down-modulates the host immune system through release of an immunosuppressive TGF-β mimic, TGM1, which is a divergent member of the CCP (Sushi) protein family. TGM1 comprises 5 domains, of which domains 1-3 (D1/2/3) bind mammalian TGF-β receptors, acting on T cells to induce Foxp3 regulatory T cells; however, the roles of domains 4 and 5 (D4/5) remain unknown. We noted that truncated TGM1, lacking D4/5, showed reduced potency. Combination of D1/2/3 and D4/5 as separate proteins did not alter potency, suggesting that a physical linkage is required and that these domains do not deliver an independent signal. Coprecipitation from cells treated with biotinylated D4/5, followed by mass spectrometry, identified the cell surface protein CD44 as a coreceptor for TGM1. Both full-length and D4/5 bound strongly to a range of primary cells and cell lines, to a greater degree than D1/2/3 alone, although some cell lines did not respond to TGM1. Ectopic expression of CD44 in nonresponding cells conferred responsiveness, while genetic depletion of CD44 abolished enhancement by D4/5 and ablated the ability of full-length TGM1 to bind to cell surfaces. Moreover, CD44-deficient T cells showed attenuated induction of Foxp3 by full-length TGM1, to levels similar to those induced by D1/2/3. Hence, a parasite protein known to bind two host cytokine receptor subunits has evolved a third receptor specificity, which serves to raise the avidity and cell type-specific potency of TGF-β signaling in mammalian cells.
Topics: Animals; Mice; Parasites; T-Lymphocytes, Regulatory; Signal Transduction; Transforming Growth Factor beta; Forkhead Transcription Factors; Mammals
PubMed: 37590410
DOI: 10.1073/pnas.2302370120 -
PLoS Pathogens Dec 2023Protein phosphatases are post-translational regulators of Toxoplasma gondii proliferation, tachyzoite-bradyzoite differentiation and pathogenesis. Here, we identify the...
Protein phosphatases are post-translational regulators of Toxoplasma gondii proliferation, tachyzoite-bradyzoite differentiation and pathogenesis. Here, we identify the putative protein phosphatase 6 (TgPP6) subunits of T. gondii and elucidate their role in the parasite lytic cycle. The putative catalytic subunit TgPP6C and regulatory subunit TgPP6R likely form a complex whereas the predicted structural subunit TgPP6S, with low homology to the human PP6 structural subunit, does not coassemble with TgPP6C and TgPP6R. Functional studies showed that TgPP6C and TgPP6R are essential for parasite growth and replication. The ablation of TgPP6C significantly reduced the synchronous division of the parasite's daughter cells during endodyogeny, resulting in disordered rosettes. Moreover, the six conserved motifs of TgPP6C were required for efficient endodyogeny. Phosphoproteomic analysis revealed that ablation of TgPP6C predominately altered the phosphorylation status of proteins involved in the regulation of the parasite cell cycle. Deletion of TgPP6C significantly attenuated the parasite virulence in mice. Immunization of mice with TgPP6C-deficient type I RH strain induced protective immunity against challenge with a lethal dose of RH or PYS tachyzoites and Pru cysts. Taken together, the results show that TgPP6C contributes to the cell division, replication and pathogenicity in T. gondii.
Topics: Animals; Humans; Mice; Catalytic Domain; Cell Cycle; Cell Division; Parasites; Protozoan Proteins; Toxoplasma; Virulence; Phosphoprotein Phosphatases
PubMed: 38091362
DOI: 10.1371/journal.ppat.1011831 -
Environmental Science and Pollution... Dec 2023Plastic pollution is now a ubiquitous feature of freshwater systems and the majority of this is fibrous. Here, we test the effects of plastic and cellulose-based fibres...
Plastic pollution is now a ubiquitous feature of freshwater systems and the majority of this is fibrous. Here, we test the effects of plastic and cellulose-based fibres (polyester, cotton, and bamboo from commercial clothing) on fish host-parasite interactions using a freshwater fish host-parasite model system (guppy Poecilia reticulata-Gyrodactylus turnbulli). For uninfected fish, polyester exposure was associated with significantly higher mortality rates compared with the other two fibre types. For infected fish, whilst polyester and cotton exposure were not associated with any significant changes to parasite burdens, fish exposed to bamboo fibres had significantly reduced maximum parasite burdens compared with fish not exposed to any fibres, indicating that the bamboo fibres and/or associated dyes conferred some degree of resistance or tolerance. Whilst unable to determine the exact nature of the chemical dyes, when testing off-host parasite survival on exposure to the fibre dyes, cotton and particularly polyester dyes were associated with higher parasite mortality compared to bamboo. Overall, we add to the growing body of evidence which shows that polyester microplastic fibres and their associated dyes can be detrimental for both fish and parasite survival, and we highlight the need for increased transparency from textile industries on the chemical identity of fabric dyes.
Topics: Animals; Parasites; Plastics; Cellulose; Trematoda; Poecilia; Polyesters; Gossypium
PubMed: 37955728
DOI: 10.1007/s11356-023-30794-0 -
Cell Reports Sep 2023We have generated a high-confidence mitochondrial proteome (MitoTag) of the Trypanosoma brucei procyclic stage containing 1,239 proteins. For 337 of these, a...
We have generated a high-confidence mitochondrial proteome (MitoTag) of the Trypanosoma brucei procyclic stage containing 1,239 proteins. For 337 of these, a mitochondrial localization had not been described before. We use the TrypTag dataset as a foundation and take advantage of the properties of the fluorescent protein tag that causes aberrant but fortuitous accumulation of tagged matrix and inner membrane proteins near the kinetoplast (mitochondrial DNA). Combined with transmembrane domain predictions, this characteristic allowed categorization of 1,053 proteins into mitochondrial sub-compartments, the detection of unique matrix-localized fucose and methionine synthesis, and the identification of new kinetoplast proteins, which showed kinetoplast-linked pyrimidine synthesis. Moreover, disruption of targeting signals by tagging allowed mapping of the mode of protein targeting to these sub-compartments, identifying a set of C-tail anchored outer mitochondrial membrane proteins and mitochondrial carriers likely employing multiple target peptides. This dataset represents a comprehensive, updated mapping of the mitochondrion.
Topics: Animals; Trypanosoma brucei brucei; Mitochondrial Proteins; Protozoan Proteins; Mitochondria; Parasites; Biology
PubMed: 37669165
DOI: 10.1016/j.celrep.2023.113083