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Current Allergy and Asthma Reports Jul 2023Helminth infections modify the natural history of allergic diseases, by either decreasing or increasing their symptoms. Several helminth components are involved in the... (Review)
Review
PURPOSE OF REVIEW
Helminth infections modify the natural history of allergic diseases, by either decreasing or increasing their symptoms. Several helminth components are involved in the increasing of the allergic response and symptoms, overcoming the concomitant immunosuppression of helminthiases. However, the role of individual IgE-binding molecules in this process remains to be defined.
RECENT FINDINGS
We updated the list of helminth allergens and IgE-binding molecules, their effects on asthma presentation, and their impact on allergy diagnosis. Data from genetic and epigenetic studies of ascariasis are analyzed. A new species-specific A. lumbricoides allergen has been discovered, with potential use in molecular diagnosis. Most helminth IgE-binding components are not officially classified as allergens in the WHO/IUIS database, although there is evidence of their influence increasing allergic manifestations. Further immunological characterization of these components is needed to better understand their mechanisms of action and evaluate the ways in which they can influence the diagnosis of allergy.
Topics: Animals; Humans; Allergens; Parasites; Immunoglobulin E; Hypersensitivity; Asthma
PubMed: 37269427
DOI: 10.1007/s11882-023-01089-8 -
Nature Jan 2024The symptoms of malaria occur during the blood stage of infection, when parasites invade and replicate within human erythrocytes. The PfPCRCR complex, containing PfRH5...
The symptoms of malaria occur during the blood stage of infection, when parasites invade and replicate within human erythrocytes. The PfPCRCR complex, containing PfRH5 (refs. ), PfCyRPA, PfRIPR, PfCSS and PfPTRAMP, is essential for erythrocyte invasion by the deadliest human malaria parasite, Plasmodium falciparum. Invasion can be prevented by antibodies or nanobodies against each of these conserved proteins, making them the leading blood-stage malaria vaccine candidates. However, little is known about how PfPCRCR functions during invasion. Here we present the structure of the PfRCR complex, containing PfRH5, PfCyRPA and PfRIPR, determined by cryogenic-electron microscopy. We test the hypothesis that PfRH5 opens to insert into the membrane, instead showing that a rigid, disulfide-locked PfRH5 can mediate efficient erythrocyte invasion. We show, through modelling and an erythrocyte-binding assay, that PfCyRPA-binding antibodies neutralize invasion through a steric mechanism. We determine the structure of PfRIPR, showing that it consists of an ordered, multidomain core flexibly linked to an elongated tail. We also show that the elongated tail of PfRIPR, which is the target of growth-neutralizing antibodies, binds to the PfCSS-PfPTRAMP complex on the parasite membrane. A modular PfRIPR is therefore linked to the merozoite membrane through an elongated tail, and its structured core presents PfCyRPA and PfRH5 to interact with erythrocyte receptors. This provides fresh insight into the molecular mechanism of erythrocyte invasion and opens the way to new approaches in rational vaccine design.
Topics: Animals; Humans; Antibodies, Neutralizing; Antigens, Protozoan; Cryoelectron Microscopy; Disulfides; Erythrocytes; Malaria Vaccines; Malaria, Falciparum; Merozoites; Multiprotein Complexes; Parasites; Plasmodium falciparum; Protozoan Proteins
PubMed: 38123677
DOI: 10.1038/s41586-023-06856-1 -
Trends in Parasitology Aug 2023For pathogenic organisms, faster rates of multiplication promote transmission success, the potential to harm hosts, and the evolution of drug resistance. Parasite... (Review)
Review
For pathogenic organisms, faster rates of multiplication promote transmission success, the potential to harm hosts, and the evolution of drug resistance. Parasite multiplication rates (PMRs) are often quantified in malaria infections, given the relative ease of sampling. Using modern and historical human infection data, we show that established methods return extraordinarily - and implausibly - large PMRs. We illustrate how inflated PMRs arise from two facets of malaria biology that are far from unique: (i) some developmental ages are easier to sample than others; (ii) the distribution of developmental ages changes over the course of infection. The difficulty of accurately quantifying PMRs demonstrates a need for robust methods and a subsequent re-evaluation of what is known even in the well-studied system of malaria.
Topics: Animals; Humans; Malaria, Falciparum; Parasites; Plasmodium falciparum; Malaria
PubMed: 37336700
DOI: 10.1016/j.pt.2023.05.006 -
Oecologia Jan 2024Understanding the ecological assembly of parasite communities is critical to characterise how changing host and environmental landscapes will alter infection dynamics...
Understanding the ecological assembly of parasite communities is critical to characterise how changing host and environmental landscapes will alter infection dynamics and outcomes. However, studies frequently assume that (a) closely related parasite species or those with identical life-history strategies are functionally equivalent, and (b) the same factors will drive infection dynamics for a single parasite across multiple host species, oversimplifying community assembly patterns. Here, we challenge these two assumptions using a naturally occurring host-parasite system, with the mussel Anodonta anatina infected by the digenean trematode Echinoparyphium recurvatum, and the snail Viviparus viviparus infected by both E. recurvatum and Echinostoma sp. By analysing the impact of temporal parasite dispersal, host species and size, and the impact of coinfection (moving from broader environmental factors to within-host dynamics), we show that neither assumption holds true, but at different ecological scales. The assumption that closely related parasites can be functionally grouped is challenged when considering dispersal to the host (i.e. larger scales), while the assumption that the same factors will drive infection dynamics for a single parasite across multiple host species is challenged when considering within-host interspecific competition (i.e. smaller scales). Our results demonstrate that host identity, parasite identity and ecological scale require simultaneous consideration in studies of parasite community composition and transmission.
Topics: Animals; Parasites; Host-Parasite Interactions; Trematoda; Snails
PubMed: 38206416
DOI: 10.1007/s00442-023-05499-3 -
Applied and Environmental Microbiology Oct 2023Temperature affects growth, metabolism, and interspecific interactions in microbial communities. Within animal hosts, gut bacterial symbionts can provide resistance to...
Temperature affects growth, metabolism, and interspecific interactions in microbial communities. Within animal hosts, gut bacterial symbionts can provide resistance to parasitic infections. Both infection and populations of symbionts can be shaped by the host body temperature. However, the effects of temperature on the antiparasitic activities of gut symbionts have seldom been explored. The -rich gut microbiota of facultatively endothermic honey bees is subject to seasonal and ontogenetic changes in host temperature that could alter the effects of symbionts against parasites. We used cell cultures of a symbiont and an important trypanosomatid gut parasite of honey bees to test the potential for temperature to shape parasite-symbiont interactions. We found that symbionts showed greater heat tolerance than parasites and chemically inhibited parasite growth via production of acids. Acceleration of symbiont growth and acid production at high temperatures resulted in progressively stronger antiparasitic effects across a temperature range typical of bee colonies. Consequently, the presence of symbionts reduced both the peak growth rate and heat tolerance of parasites. Substantial changes in parasite-symbiont interactions were evident over a temperature breadth that parallels changes in diverse animals exhibiting infection-related fevers and the amplitude of circadian temperature variation typical of endothermic birds and mammals, implying the frequent potential for temperature to alter symbiont-mediated resistance to parasites in endo- and ectothermic hosts. Results suggest that the endothermic behavior of honey bees could enhance the impacts of gut symbionts on parasites, implicating thermoregulation as a reinforcer of core symbioses and possibly microbiome-mediated antiparasitic defense. IMPORTANCE Two factors that shape the resistance of animals to infection are body temperature and gut microbiota. However, temperature can also alter interactions among microbes, raising the question of whether and how temperature changes the antiparasitic effects of gut microbiota. Honey bees are agriculturally important hosts of diverse parasites and infection-mitigating gut microbes. They can also socially regulate their body temperatures to an extent unusual for an insect. We show that high temperatures found in honey bee colonies augment the ability of a gut bacterial symbiont to inhibit the growth of a common bee parasite, reducing the parasite's ability to grow at high temperatures. This suggests that fluctuations in colony and body temperatures across life stages and seasons could alter the protective value of bees' gut microbiota against parasites, and that temperature-driven changes in gut microbiota could be an underappreciated mechanism by which temperature-including endothermy and fever-alters animal infection.
Topics: Bees; Animals; Parasites; Temperature; Microbiota; Gastrointestinal Microbiome; Bacteria; Lactobacillus; Antiparasitic Agents; Mammals
PubMed: 37791764
DOI: 10.1128/aem.01023-23 -
PLoS Pathogens Nov 2023Signalling pathways in malaria parasite remain poorly defined and major reason for this is the lack of understanding of the function of majority of parasite protein...
Signalling pathways in malaria parasite remain poorly defined and major reason for this is the lack of understanding of the function of majority of parasite protein kinases and phosphatases in parasite signalling and its biology. In the present study, we have elucidated the function of Protein Kinase 2 (PfPK2), which is known to be indispensable for the survival of human malaria parasite Plasmodium falciparum. We demonstrate that it is involved in the invasion of host erythrocytes, which is critical for establishing infection. In addition, PfPK2 may also be involved in the maturation of the parasite post-invasion. PfPK2 regulates the release of microneme proteins like Apical Membrane Antigen 1 (AMA1), which facilitates the formation of Tight Junction between the merozoite and host erythrocyte- a key step in the process of invasion. Comparative phosphoproteomics studies revealed that PfPK2 may be involved in regulation of several key proteins involved in invasion and signalling. Furthermore, PfPK2 regulates the generation of cGMP and the release of calcium in the parasite, which are key second messengers for the process of invasion. These and other studies have shed light on a novel signalling pathway in which PfPK2 acts as an upstream regulator of important cGMP-calcium signalling, which plays an important role in parasite invasion.
Topics: Animals; Humans; Protein Kinases; Protozoan Proteins; Parasites; Calcium; Plasmodium falciparum; Erythrocytes
PubMed: 37988347
DOI: 10.1371/journal.ppat.1011770 -
MSphere Oct 2023Malaria parasites modify their host erythrocyte in multiple ways, leading to changes in the deformability, adhesiveness, and permeability of the host erythrocyte. Most...
Malaria parasites modify their host erythrocyte in multiple ways, leading to changes in the deformability, adhesiveness, and permeability of the host erythrocyte. Most of these changes are mediated by proteins exported from the parasite to the host erythrocyte, where these proteins interact with the host cell cytoskeleton or form complexes in the plasma membrane of the infected erythrocyte. In addition, malaria parasites induce the formation of membranous compartments-the parasitophorous vacuole, the tubovesicular network (TVN), the Maurer's clefts and small vesicles-within the infected erythrocyte, a cell that is normally devoid of internal membranes. After infection, changes also occur in the composition and asymmetry of the erythrocyte plasma membrane. Although many aspects of the mechanism of export of parasite proteins have become clear, the mechanism by which these membranous compartments are formed and expanded is almost entirely unknown. To determine whether parasite-derived phospholipids play a part in these processes, we applied a metabolic labeling technique that allows phosphatidylcholine to be labeled with a fluorophore. As the host erythrocyte cannot synthesize phospholipids, within infected erythrocytes, only parasite-derived phosphatidylcholine will be labeled with this technique. The results revealed that phosphatidylcholine produced by the parasite is distributed throughout the infected erythrocyte, including the TVN and the erythrocyte plasma membrane, but not Maurer's clefts. Interestingly, labeled phospholipids were also detected in the erythrocyte plasma membrane very soon after invasion of the parasites, indicating that the parasite may add phospholipids to the host erythrocyte during invasion. IMPORTANCE Here, we describe a previously unappreciated way in which the malaria parasite interacts with the host erythrocyte, namely, by the transfer of parasite phospholipids to the erythrocyte plasma membrane. This likely has important consequences for the survival of the parasite in the host cell and the host organism. We show that parasite-derived phospholipids are transferred from the parasite to the host erythrocyte plasma membrane and that other internal membranes that are produced after the parasite has invaded the cell are produced, at least in part, using parasite-derived phospholipids. The one exception to this is the Maurer's cleft, a membranous organelle that is involved in the transport of parasite proteins to the surface of the erythrocyte. This reveals that the Maurer's cleft is produced in a different manner than the other parasite-induced membranes. Overall, these findings provide a platform for the study of a new aspect of the host-parasite interaction.
Topics: Animals; Humans; Parasites; Phosphatidylcholines; Plasmodium falciparum; Erythrocytes; Erythrocyte Membrane; Malaria
PubMed: 37606582
DOI: 10.1128/msphere.00131-23 -
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 -
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