Frontiers in parasitology最新文献

{"title":"Malaria and associated factors among under-five children in Borena pastoral communities, southern Ethiopia.","authors":"Alqeer Aliyo, Wako Golicha, Anteneh Fikrie","doi":"10.3389/fpara.2024.1438218","DOIUrl":"10.3389/fpara.2024.1438218","url":null,"abstract":"<p><strong>Background: </strong>Malaria continues to be an important threat to public health and infects millions of children under 5 years of age each year. Although Ethiopia has set targets for at-risk group interventions to eradicate and manage malaria, the illness is still a serious public health problem in areas where it is endemic, especially in the unique lowlands in the Borena zone.</p><p><strong>Objective: </strong>This study aimed to determine the prevalence of malaria and associated factors among children in Borena's pastoral communities, Oromia Regional State, southern Ethiopia, in 2022.</p><p><strong>Methods: </strong>A community-based cross-sectional study was conducted from 1 March to 30 April 2022 among 437 randomly selected households with children under 5 years of age in pastoral communities in the Borena zone. Data were collected through face-to-face interviews with structured and pretested questionnaires and blood sample examination using microscopy. Thick and thin blood smears were prepared and examined under a microscope at a health center to confirm malaria cases. The data were analyzed using SPSS version 25. Bivariate and multivariable logistic regression analyses were used to identify factors associated with malaria, and a <i>p</i>-value <0.05 was used to declare statistical significance.</p><p><strong>Result: </strong>The prevalence of malaria among children under 5 years of age was 27.8% (95% CI = 23.5-32.1), and the prevalence rates of <i>Plasmodium falciparum</i>, <i>Plasmodium vivax</i>, and mixed malaria were 68.4%, 25.6%, and 6%, respectively. Regarding the proportion of malaria among age groups, 81% of children under 5 years of age between 48 and 59 months were malaria-positive. In this study, fever within the last week (AOR = 13.34, 95% CI = 6.37-27.95) and not sleeping under insecticide-treated nets (ITNs) (AOR = 3.10, 95% CI =1.95-4.92) were significantly associated with malaria. The age of the children was negatively associated with malaria prevalence.</p><p><strong>Conclusion: </strong>The prevalence of malaria among children under 5 years old was high during the rainy season in this pastoral region of Ethiopia. Factors such as fever within the last week and not sleeping in insecticide-treated nets were significantly associated with malaria. Therefore, to reduce malaria-related infections and deaths among children under 5 years of age, the government ought to enhance the availability and utilization of insecticide-treated nets (ITNs).</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"3 ","pages":"1438218"},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From laboratory to clinical practice: an update of the immunological and molecular tools for neurocysticercosis diagnosis","authors":"L. Toribio, J. Bustos, Hector H. Garcia","doi":"10.3389/fpara.2024.1394089","DOIUrl":"https://doi.org/10.3389/fpara.2024.1394089","url":null,"abstract":"Neurocysticercosis (NCC) is caused by the invasion of Taenia solium larvae in the central nervous system (CNS) and stands as the predominant cause of epilepsy and other neurological disorders in many developing nations. NCC diagnosis is challenging because it relies on brain imaging exams (CT or MRI), which are poorly available in endemic rural or resource-limited areas. Moreover, some NCC cases cannot be easily detected by imaging, leading to inconclusive results. Multiple laboratory assays, principally immunological, have been developed to support the diagnosis and/or monitor the treatment efficacy, but its production can be costly, laborious, and non-globally accessible because they depend on parasite material. Therefore, recent advances have been focused on the implementation of recombinant or synthetic antigens as well as monoclonal antibodies for NCC immunodiagnosis purposes. Similarly, molecular diagnosis has been explored, obtaining promising results. Here we described the recent progress in the development of immunological and molecular diagnostic tools for NCC diagnosis over the past 13 years, discussing their potential application to address important challenges and how to focus future directions to improve NCC diagnosis with emphasis on enhance accessibility and the importance of test validation to provide an adequate support for clinical decisions.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"12 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141715183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Nuttalliella namaqua</i> Bedford, 1931, a sole extant species of the genus <i>Nuttalliella</i> - a scoping review.","authors":"Maphuti Betty Ledwaba, Dikeledi Petunia Malatji","doi":"10.3389/fpara.2024.1401351","DOIUrl":"10.3389/fpara.2024.1401351","url":null,"abstract":"<p><p><i>Nuttalliella namaqua</i> Bedford, 1931 is the sole extant tick species that belongs to the genus and family <i>Nuttalliella</i> and Nuttalliellidae respectively. With the characteristics that are respectively distinctive to hard and soft ticks, it is regarded as the species closest to the ancestral lineage of ticks as well as the missing link between the Argasidae and Ixodidae families. In this review, literature search of the articles reporting on <i>N. namaqua</i> was done in Google Scholar and PubMed databases. After relevance and eligibility screening, 12 articles were deemed eligible and appraised. The results showed that <i>N. namaqua</i> was respectively distinct to limited regions of Africa such as Botswana, Namibia, Mozambique, South Africa and Tanzania. The review also indicated that <i>N. namaqua</i> was collected from murid rodents, African Savanna hare, scrub hare, elephant shrews, rock hyraxes, black backed jackal, lizards and off-host in locations that include under a stone, rock crevices, on a rock wall and respectively in the nests of an eagle and a lesser striped swallow. Irrespective of all the reports, natural hosts of the nymphs are still not clearly defined. Numerous phylogeny studies have reported Nuttalliellidae as the sister-lineage to Argasidae and Ixodidae tick families. Moreover, a recent report indicated that the similarities between Nuttalliellidae and the fossil families Deinocrotonidae and Legionaris award them to be merged into one family, preferably Nuttalliellidae Thus, further research on this family, will perhaps provide more knowledge about its unclear distribution, life cycle as well as the evolution of ticks in general.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"3 ","pages":"1401351"},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptome analysis reveals molecular targets of erythrocyte invasion phenotype diversity in natural Plasmodium falciparum isolates from Cameroon","authors":"Ines A. Ngoh, Karim Mane, Jarra Manneh, F. Bojang, A. Jawara, Theresia N. Akenji, D. Anong, Umberto D’Alessandro, A. Amambua-Ngwa","doi":"10.3389/fpara.2024.1370615","DOIUrl":"https://doi.org/10.3389/fpara.2024.1370615","url":null,"abstract":"Further understanding of the molecular mediators of alternative RBC invasion phenotypes in endemic malaria parasites will support malaria blood-stage vaccine or drug development. This study investigated the prevalence of sialic acid (SA)-dependent and SA-independent RBC invasion pathways in endemic Plasmodium falciparum parasites from Cameroon and compared the schizont stage transcriptomes in these two groups to uncover the wider repertoire of transcriptional variation associated with the use of alternative RBC invasion pathway phenotypes. A two-color flow cytometry-based invasion-inhibition assay against RBCs treated with neuraminidase, trypsin, and chymotrypsin and deep RNA sequencing of schizont stages harvested in the first ex vivo replication cycle in culture were employed in this investigation. RBC invasion phenotypes were determined for 63 isolates from asymptomatic children with uncomplicated malaria. Approximately 80% of the isolates invaded neuraminidase-treated but not chymotrypsin-treated RBCs, representing SA-independent pathways of RBC invasion. The schizont transcriptome profiles of 16 isolates with invasion phenotypes revealed a total of 5,136 gene transcripts, with 85% of isolates predicted at schizont stages. Two distinct transcriptome profile clusters belonging to SA-dependent and SA-independent parasites were obtained by data reduction with principal component analysis. Differential analysis of gene expression between the two clusters implicated, in addition to the well-characterized adhesins, the upregulation of genes encoding proteins mediating merozoite organelle discharges as well as several conserved, virulent, merozoite-associated, and exported proteins. The latter majority have been shown to have structural and physiological relevance to RBC surface remodeling and immune evasion in malaria and thus have potential as anti-invasion targets.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"21 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141102867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next step towards point-of-care molecular diagnosis of female genital schistosomiasis (FGS): evaluation of an instrument-free LAMP procedure","authors":"Kim J. M. van Bergen, E. Brienen, Bodo S. Randrianasolo, C. Ramarokoto, P. Leutscher, E. F. Kjetland, Angela van Diepen, Floris Dekker, V. Saggiomo, A. Velders, Lisette van Lieshout","doi":"10.3389/fpara.2024.1297310","DOIUrl":"https://doi.org/10.3389/fpara.2024.1297310","url":null,"abstract":"Detection of Schistosoma spp. DNA in gynaecological samples by quantitative real-time polymerase chain reaction (qPCR) is considered to be the reference diagnostic test for female genital schistosomiasis (FGS). However, qPCR needs expensive laboratory procedures and highly trained technicians. Loop-mediated amplification (LAMP) is a more field-friendly isothermal procedure for the detection of parasite-specific DNA, but it still requires electrically powered equipment. Here, we validated a Schistosoma haematobium-specific Sh-LAMP procedure and tested a fully instrument-free isothermal amplification using a novel low-cost, and reusable Temperature-cup (T-cup) device. Specific primers were selected based on published assays, targeting the ribosomal intergenic spacer (IGS) region of S. haematobium. Technical validation of the IGS-Sh-LAMP was performed using 20 negative controls, including DNA extracts of soil-transmitted helminths and S. mansoni, and a 10-fold dilution series (100–10−3) of DNA extracted from a single S. haematobium egg (n=4). For clinical validation, the IGS-Sh-LAMP was tested on 125 DNA samples extracted from vaginal swabs of a previous FGS study in Madagascar. Results were compared with the quantification cycle value (Cq) of the standard ITS-2 targeting qPCR. Single S. haematobium egg DNA up to a 10–2 dilution and an ITS-2 Cq <35 tested positive in the IGS-Sh-LAMP. The specificity was found to be excellent (100%). In the clinical samples, IGS-Sh-LAMP showed comparable results with the qPCR, with 35.2% and 33.6% positives, respectively, and a concordance of 79.2% (99/125). Of the 12 false-negatives, 5 corresponded to the 7 qPCR positive samples with very low DNA levels (Cq ≥35). On the other hand, IGS-Sh-LAMP detected 14 additional cases that were not detected by qPCR. The T-cup IGS-Sh-LAMP performance was evaluated in a representative sub-selection (n=10) of IGS-Sh-LAMP positive clinical samples. The T-cup IGS-Sh-LAMP was found to be a very user-friendly method, but in different runs, it missed 1 to 4 of the 10 IGS-Sh-LAMP positive samples, specifically those with a low DNA load. Our results show that the IGS-Sh-LAMP is a suitable alternative to the ITS-2 qPCR for the diagnosis of FGS in gynaecological samples, with high potential for the T-cup as a fully instrument-free isothermal amplification device for point-of-care diagnosis in low-resource settings.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"124 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140985307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of potent schistosomicidal compounds predicted as type II-kinase inhibitors against <i>Schistosoma mansoni</i> c-Jun N-terminal kinase SMJNK.","authors":"Bernardo P Moreira, Sandra G Gava, Simone Haeberlein, Sophie Gueye, Ester S S Santos, Michael H W Weber, Tigran M Abramyan, Christoph G Grevelding, Marina M Mourão, Franco H Falcone","doi":"10.3389/fpara.2024.1394407","DOIUrl":"10.3389/fpara.2024.1394407","url":null,"abstract":"<p><strong>Introduction: </strong>Schistosomiasis has for many years relied on a single drug, praziquantel (PZQ) for treatment of the disease. Immense efforts have been invested in the discovery of protein kinase (PK) inhibitors; however, given that the majority of PKs are still not targeted by an inhibitor with a useful level of selectivity, there is a compelling need to expand the chemical space available for synthesizing new, potent, and selective PK inhibitors. Small-molecule inhibitors targeting the ATP pocket of the catalytic domain of PKs have the potential to become drugs devoid of (major) side effects, particularly if they bind selectively. This is the case for type II PK inhibitors, which cause PKs to adopt the so-called DFG-out conformation, corresponding to the inactive state of the enzyme.</p><p><strong>Methods: </strong>The goal was to perform a virtual screen against the ATP pocket of the inactive JNK protein kinase. After virtually screening millions of compounds, Atomwise provided 85 compounds predicted to target c-Jun N-terminal kinase (JNK) as type II inhibitors. Selected compounds were screened <i>in vitro</i> against larval stage (schistosomula) of <i>S. mansoni</i> using the XTT assay. Adult worms were assessed for motility, attachment, and pairing stability. Active compounds were further analyzed by molecular docking against SmJNK.</p><p><strong>Results: </strong>In total, 33 compounds were considered active in at least one of the assays, and two compounds were active in every <i>in vitro</i> screening assay. The two most potent compounds presented strong effects against both life stages of the parasite, and microscopy analysis showed phenotypic alterations on the tegument, in the gonads, and impairment of cell proliferation.</p><p><strong>Conclusion: </strong>The approach to screen type II kinase inhibitors resulted in the identification of active compounds that will be further developed against schistosomiasis.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"3 ","pages":"1394407"},"PeriodicalIF":0.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro and in vivo antimalarial activities of the ethanol extract of Erythrina sigmoidea stem bark used for the treatment of malaria in the Western Region of Cameroon","authors":"Tientcheu Noutong Jemimah Sandra, Noumedem Anangmo Christelle Nadia, Yamssi Cédric, Gamago Nkadeu Guy-Armand, Mounvera Abdel Azizi, Ngouyamsa Nsapkain Aboubakar Sidiki, Tako Djimefo Alex Kevin, V. Payne, Haibo Hu","doi":"10.3389/fpara.2024.1359442","DOIUrl":"https://doi.org/10.3389/fpara.2024.1359442","url":null,"abstract":"Malaria is one of the leading causes of morbidity and/or mortality in tropical Africa. The spread and development of resistance to chemical antimalarial drugs and the relatively high cost of the latter are problems associated with malaria control and are reasons to promote the use of plants to meet healthcare needs to treat malaria. The aim of this study was to evaluate antiplasmodial activities of extracts of Erythrina sigmoidea (Mah quat), which is traditionally used for the treatment of malaria in the western region of Cameroon.The ethanol extract of E. sigmoidea stem bark was obtained through the maceration process using 95% ethanol, while the aqueous extract was prepared by infusion. The in vitro antiplasmodial effect of extracts against P. falciparum chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) strains was determined using the Trager and Jensen method. On the other hand, the in vivo antimalarial activity of the extract was evaluated in mice infected with Plasmodium berghei strain NK65 using the Peters’ 4-day suppressive test and Ryley test (curative test). A total of 36 mice were used, subdivided into six groups of six mice each: one normal control, a negative control, a positive control, and three other groups for the tested product. Blood samples were collected on the 10th day of each test for hematological parameters.The aqueous extract had an in vitro antiplasmodial activity against the chloroquine-sensitive strain with an IC50 of 29.51 ± 3.63 µg/mL and against the chloroquine-resistant strain with an IC50 of 35.23 ± 3.17 µg/mL. The highest in vitro antiplasmodial activity was observed with the ethanol extract against the chloroquine-sensitive strain with an IC50 of 6.44 ± 0.08 µg/mL and against the chloroquine-resistant strain with an IC50 of 7.53 ± 0.22 µg/mL. The ethanol extract demonstrated suppressive activity in vivo with reduction rates of 87.69%, 86.79%, and 81.08% at doses of 500 mg/kg, 250 mg/kg, and 125 mg/kg, respectively; and curative activity in vivo with reduction rates of 80%, 78.5%, and 77.5% at doses of 500 mg/kg, 250 mg/kg, and 125 mg/kg, respectively. The number of white blood cells in the negative control (44.55 ± 5.02 103/µL) was higher compared to the other groups. As for the red blood cells, we observed a massive destruction of the latter in the infected and untreated group (5.82 ± 1.50 106/µL) compared to the infected and ethanol extract-treated groups (8.74 ± 1.57 106/µL for 500 mg/kg, 7.54 ± 1.77 106/µL for 250 mg/kg, and 8.9 ± 1.50 106/µL for 125 mg/kg).This study provides scientific data on the use of E. sigmoidea by the local population for the treatment of malaria. It shows that E. sigmoidea has antiplasmodial activity, and we also see that there are differences between the parameters that we have in the treated groups and those of the untreated group. However, toxicity tests are necessary to assess its safety.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"29 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140722517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic variation of the Plasmodium falciparum circumsporozoite protein in parasite isolates from Homabay County in Kenya","authors":"M. Maina, S. Musundi, Josiah O. Kuja, Harrison Waweru, Daniel Kiboi, B. Kanoi, Jesse Gitaka","doi":"10.3389/fpara.2024.1346017","DOIUrl":"https://doi.org/10.3389/fpara.2024.1346017","url":null,"abstract":"The Plasmodium falciparum Circumsporozoite Protein (PfCSP) has been used in developing the RTS,S, and R21 malaria vaccines. However, genetic polymorphisms within Pfcsp compromise the effectiveness of the vaccine. Thus, it is essential to continuously assess the genetic diversity of Pfcsp, especially when deploying it across different geographical regions. In this study, we assessed the genetic diversity of the Pfcsp on isolates from Homabay County, a malaria-endemic region in western Kenya, and compared it against other isolates from Kenya. We extracted DNA from 27 microscopically confirmed P. falciparum positive samples and conducted Illumina sequencing to generate paired-end short reads. The sequences were then mapped to the Pf3D7 reference genome, and genetic variation was analyzed using bcftools. Additionally, we retrieved isolates from two other malaria-endemic regions in Kenya, Kisumu (n=58) and Kilifi (n=596), from MalariaGEN version 7 and compared their genetic diversity and natural selection. We also evaluated the predicted binding affinities for HLA class I and II supertype alleles for the identified haplotypes using NetMHCpan and NetMHCIIpan. Our results show that the N-terminal of PfCSP was relatively conserved with a notable mutation at A98G across all isolates. The number of NANP repeats varied across the three Kenyan sites within the central repeat region. Furthermore, the C-terminal region showed polymorphism within the Th2R and Th3R regions. Haplotype network analysis of the Kenyan isolates revealed 69 haplotypes, with the 3D7 reference being found in the most prevalent haplotype. When assessing the predicted binding affinities between supertypes in HLA class I and II with the identified haplotypes, we observed stronger predicted binding affinities to multiple haplotypes except for those containing the 3D7 reference. The results suggest the need to take into account the existing changes occurring in Pfcsp while developing malaria vaccines.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"6 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140728627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory properties of Leishmania tarentolae extracellular vesicles containing the Spike protein of SARS-CoV-2","authors":"Ana Catalina Medina, Hamlet Adolfo Acevedo Ospina, Albert Descoteaux","doi":"10.3389/fpara.2024.1306478","DOIUrl":"https://doi.org/10.3389/fpara.2024.1306478","url":null,"abstract":"Extracellular vesicles released by the protozoan parasite Leishmania display immunomodulatory properties towards mammalian immune cells. In this study, we have evaluated the potential of extracellular vesicles derived from the non-pathogenic protozoan Leishmania tarentolae towards the development of a vaccine adjuvant. As a proof of concept, we expressed in L. tarentolae a codon-optimized SARS-CoV-2 Spike protein fused to the L. mexicana secreted acid phosphatase signal peptide in the N-terminal and to a 6×-His stretch in the C-terminal. Extracellular vesicles released by the engineered L. tarentolae were isolated by ultracentrifugation and fast protein liquid chromatography and were characterized via nanoparticle tracking analysis and transmission electron microscopy. The recombinant S protein was present in extracellular vesicles released by L. tarentolae, as determined by Western blot analyses and immunoelectron microscopy. Next, we evaluated the immunomodulatory potential of extracellular vesicles containing the S protein towards bone-marrow-derived macrophages and bone-marrow-derived dendritic cells. Our data show that in bone-marrow-derived dendritic cells, extracellular vesicles containing the S protein induced an increased expression of proinflammatory genes compared to plain extracellular vesicles whereas the opposite was observed in bone-marrow-derived macrophages. These findings reveal the immunomodulatory potential of L. tarentolae extracellular vesicles and provide a proof of concept that they can be used as adjuvant in the context of dendritic cell stimulation.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"208 S643","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140730842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EhVps35, a retromer component, is involved in the recycling of the EhADH and Gal/GalNac virulent proteins of Entamoeba histolytica","authors":"Joselin Díaz-Valdez, R. Javier‐Reyna, Sarita Montaño, Daniel Talamás-Lara, Esther Orozco","doi":"10.3389/fpara.2024.1356601","DOIUrl":"https://doi.org/10.3389/fpara.2024.1356601","url":null,"abstract":"The retromer is a highly conserved eukaryotic complex formed by the cargo selective complex (CSC) and the sorting nexin (SNX) dimer subcomplexes. Its function is protein recycling and recovery from the endosomes to conduct the target molecules to the trans-Golgi network or the plasma membrane. The protozoan responsible for human amoebiasis, Entamoeba histolytica, exhibits an active membrane movement and voracious phagocytosis, events in which the retromer may be fully involved. In this work, we studied the structure of EhVps35 the central member of the CSC retromeric subcomplex as it binds EhVps26 and EhVps29, the other two CSC members, allowing the position of the retromer in the membranes. We also studied the EhVps35 role in the recycling of virulence proteins, particularly those involved in phagocytosis. Confocal microscopy assays revealed that EhVps35 is located in the plasmatic and endosomal membranes and in the phagocytic cups and channels. In addition, it follows the target cell from the moment it is in contact with the trophozoites. Molecular docking analyses, immunoprecipitation assays, and microscopy studies revealed that EhVps35 interacts with the EhADH, Gal/GalNac lectin, and actin proteins. In addition, experimental evidence indicated that it recycles surface proteins, particularly EhADH and Gal/GalNac proteins, two molecules highly involved in virulence. Knockdown of the Ehvps35 gene induced a decrease in protein recycling, as well as impairments in the efficiency of adhesion and the rate of phagocytosis. The actin cytoskeleton was deeply affected by the Ehvps35 gene knockdown. In summary, our results revealed the participation of EhVps35 in protein recycling and phagocytosis. Furthermore, altogether, our results demonstrated the concert of finely regulated molecules, including EhVps35, EhADH, Gal/GalNac lectin, and actin, in the phagocytosis of E. histolytica.","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"102 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140381115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}