Host-parasite Interactions Research Articles

Four new species of Cichlidogyrus (Platyhelminthes, Monopisthocotyla, Dactylogyridae) from Lake Victoria haplochromine cichlid fishes, with the redescription of C. bifurcatus and C. longipenis.

African cichlids are model systems for evolutionary studies and host-parasite interactions, because of their adaptive radiations and because they harbour many species of monogenean parasites with high host-specificity. Five locations were sampled in southern Lake Victoria: gill-infecting monogeneans were surveyed from 18 cichlid species belonging to this radiation superflock and two others representing two older and distantly related lineages. We found one species of Gyrodactylidae, Gyrodactylus sturmbaueri Vanhove, Snoeks, Volckaert & Huyse, 2011, and seven species of Dactylogyridae. Four are described herein: Cichlidogyrus pseudodossoui n. sp., Cichlidogyrus nyanza n. sp., Cichlidogyrus furu n. sp., and Cichlidogyrus vetusmolendarius n. sp. Another Cichlidogyrus species is reported but not formally described (low number of specimens, morphological similarity with C. furu n. sp.). Two other species are redescribed: C. bifurcatus Paperna, 1960 and C. longipenis Paperna & Thurston, 1969. Our results confirm that the monogenean fauna of Victorian littoral cichlids displays lower species richness and lower host-specificity than that of Lake Tanganyika littoral cichlids. In C. furu n. sp., hooks V are clearly longer than the others, highlighting the need to re-evaluate the current classification system that considers hook pairs III-VII as rather uniform. Some morphological features of C. bifurcatus, C. longipenis, and C. nyanza n. sp. suggest that these are closely related to congeners that infect other haplochromines. Morphological traits indicate that representatives of Cichlidogyrus colonised Lake Victoria haplochromines or their ancestors at least twice, which is in line with the Lake Victoria superflock being colonised by two cichlid tribes (Haplochromini and Oreochromini).

Extracellular vesicles.

Cells, pathogens, and other systems release extracellular vesicles (EVs). The particles promote intercellular communication and contain proteins, lipids, RNA and DNA. Initially considered to be cellular waste in the twentieth century, EVs were becoming recognized for their function in biological communication and control. EVs are divided into many subtypes: exosomes, microvesicles, and apoptotic bodies. Exosomes form in the late endosome/multivesicular body and are released when the compartments fuse with the plasma membrane. Microvesicles are generated by direct budding of the plasma membrane, whereas apoptotic bodies are formed after cellular apoptosis. The new guideline for EVs that describes alternate nomenclature for EVs. The particles modulate the immune response by affecting both innate and adaptive immunity, and their specific the structure allows them to be used as biomarkers to diagnose a variety of diseases. EVs have a wide range of applications, for example, delivery systems for medications and genetic therapies because of their ability to convey specific cellular material. In anti-tumor therapy, EVs deliver therapeutic chemicals to tumor cells. The EVs promote transplant compatibility and reduce organ rejection. Host-parasite interactions, therapeutic and diagnostic for cancer, cardiovascular disease, cardiac tissue regeneration, and the treatment of neurological diseases such as Alzheimer's and Parkinson's. The study of EVs keeps on expanding, revealing new functions and beneficial options. EVs have the potential to change drug delivery, diagnostics, and specific therapeutics, creating a new frontier in biomedical.

Monitoring of Lipid Fluxes Between Host and Plastid-Bearing Apicomplexan Parasites.

Apicomplexan parasites are unicellular eukaryotes responsible for major human diseases such as malaria and toxoplasmosis, which cause massive social and economic burden. Toxoplasmosis, caused by Toxoplasma gondii, is a global chronic infectious disease affecting ~1/3 of the world population and is a major threat for any immunocompromised patient. To date, there is no efficient vaccine against these parasites and existing treatments are threatened by rapid emergence of parasite resistance. Throughout their life cycle, Apicomplexa require large amount of nutrients, especially lipids for propagation and survival. Understanding lipid acquisition is key to decipher host-parasite metabolic interactions. Parasite membrane biogenesis relies on a combination of (a) host lipid scavenging, (b) de novo lipid synthesis in the parasite, and (c) fluxes of lipids between host and parasite and within. We recently uncovered that parasite need to store the host-scavenged lipids to avoid their toxic accumulation and to mobilize them for division. How can parasites orchestrate the many lipids fluxes essential for survival? Here, we developed metabolomics approaches coupled to stable isotope labelling to track, monitor, and quantify fatty acid and lipids fluxes between the parasite, its human host cell, and its extracellular environment to unravel the complex lipid fluxes in any physiological environment the parasite could meet.

Transcriptional Profiling of the Rabbit Liver Infected With Eimeria stiedae Reveals Dynamic Host Cell Responses During the Induction and Resolution of Cholangitis

Eimeria stiedae is one of the few eukaryotic pathogens that exclusively infect the liver and serves as a good model to study the host–pathogen interactions in this vital organ. In this study, we show that rabbits infected with E. stiedae develop severe but self‐healing cholangitis. RNA‐seq analysis of the liver gene expression landscapes over the long course of E. stiedae infection identified 912 differentially expressed genes (DEGs) in the prepatent period (794 up‐ and 118 downregulated genes), 2889 DEGs in the early oocyst shedding period (1870 up‐ and 1019 downregulated genes), 2859 DEGs in the peak oocyst shedding period (1923 up‐ and 936 downregulated genes), and 327 DEGs in the recovery period (164 up‐ and 163 downregulated genes). Combined with pathological observations, we identified dynamic changes in host–parasite interactions involving multiple pathways. They showed that E. stiedae infection induced full‐blown inflammatory, Th1 and Th17 immune responses at all time points. This was associated with the strong innate immune responses during the prepatent period, including increased Toll‐like and NOD‐like receptor signaling. Despite mounting several damage control and repair responses, such as PI3K‐Akt signaling, Ras signaling, and extracellular matrix‐receptor interactions, the liver underwent severe metabolic dysfunction, oxidative damage, and coagulopathy after patency and at peak infection, possibly as a result of suppressed peroxisome activities and downregulated PPAR signaling. These responses largely disappeared during late infection, suggesting that the liver self‐heals after severe cholangitis. These data provide new insights into host–pathogen interactions during Eimeria infection and improve our understanding of the pathogenesis of parasitic cholangitis.

The depressed river mussel Pseudanodonta complanata as an occasional host for the European bitterling Rhodeus amarus

This study explores the utilisation of European freshwater mussels as hosts by the European bitterling (Rhodeus amarus) at their current sympatric occurrence range. Our study confirms Pseudanodonta complanata as a suitable, occasional host for bitterling. The spawning relationship of R. amarus with freshwater mussels has physiological costs for the hosts, leading to resource competition and potential negative effects on host fertility. Further research is needed to assess the dynamics of host-parasite interactions, mussel adaptations to prevent parasitism, and the consequences of the bitterling recent and possible future expansion in Europe for mussel populations.

Global distribution patterns and geographic range of Cymothoa Fabricius, 1793 (Isopoda: Cymothoidae) associated with host fish.

Over recent years, fish parasites of the genus Cymothoa Fabricius, 1793, have received increased attention due to both their ecological and their economic importance to aquaculture and fishery. As the studies about Cymothoa have increased this improve our understanding on the host specificity and distribution of these parasites. The aim of this paper was to review the current global geographic distribution, distribution patterns and parasite-host interactions patterns of Cymothoa spp. associated with fish from marine and brackish water bodies around the world. A total of 144 samples were analyzed, from which 23 species of Cymothoa were found parasitizing 84 teleost fish species of 35 families and 20 orders. Most of these parasites were found in the mouth of the host fish, including in wild fish. The highest occurrence of parasites was found in host species belonging to the families Carangidae and Lutjanidae. Host specificity was an important factor in the geographic distribution of Cymothoa species as also environmental temperature. Cymothoa indica, Cymothoa exigua and Cymothoa excisa were the species with lowest specificity for host family and widest geographic distribution.

Targeting and activation of macrophages in leishmaniasis. A focus on iron oxide nanoparticles.

Macrophages play a pivotal role as host cells for Leishmania parasites, displaying a notable functional adaptability ranging from the proinflammatory, leishmanicidal M1 phenotype to the anti-inflammatory, parasite-permissive M2 phenotype. While macrophages can potentially eradicate amastigotes through appropriate activation, Leishmania employs diverse strategies to thwart this activation and redirect macrophages toward an M2 phenotype, facilitating its survival and replication. Additionally, a competition for iron between the two entities exits, as iron is vital for both and is also implicated in macrophage defensive oxidative mechanisms and modulation of their phenotype. This review explores the intricate interplay between macrophages, Leishmania, and iron. We focus the attention on the potential of iron oxide nanoparticles (IONPs) as a sort of immunotherapy to treat some leishmaniasis forms by reprogramming Leishmania-permissive M2 macrophages into antimicrobial M1 macrophages. Through the specific targeting of iron in macrophages, the use of IONPs emerges as a promising strategy to finely tune the parasite-host interaction, endowing macrophages with an augmented antimicrobial arsenal capable of efficiently eliminating these intrusive microbes.

Proteomics Applications in Toxoplasma gondii: Unveiling the Host-Parasite Interactions and Therapeutic Target Discovery.

Toxoplasma gondii, a protozoan parasite with the ability to infect various warm-blooded vertebrates, including humans, is the causative agent of toxoplasmosis. This infection poses significant risks, leading to severe complications in immunocompromised individuals and potentially affecting the fetus through congenital transmission. A comprehensive understanding of the intricate molecular interactions between T. gondii and its host is pivotal for the development of effective therapeutic strategies. This review emphasizes the crucial role of proteomics in T. gondii research, with a specific focus on host-parasite interactions, post-translational modifications (PTMs), PTM crosstalk, and ongoing efforts in drug discovery. Additionally, we provide an overview of recent advancements in proteomics techniques, encompassing interactome sample preparation methods such as BioID (BirA*-mediated proximity-dependent biotin identification), APEX (ascorbate peroxidase-mediated proximity labeling), and Y2H (yeast two hybrid), as well as various proteomics approaches, including single-cell analysis, DIA (data-independent acquisition), targeted, top-down, and plasma proteomics. Furthermore, we discuss bioinformatics and the integration of proteomics with other omics technologies, highlighting its potential in unraveling the intricate mechanisms of T. gondii pathogenesis and identifying novel therapeutic targets.

A Structural Analysis of Host-Parasite Interactions in Achatina fulica (Giant African Snail) Infected with Angiostrongylus cantonensis.

Angiostrongylus cantonensis is a nematode parasite that resides in the pulmonary arteries of rodents, serving as its definitive hosts. The life cycle involves several species of non-marine gastropods as intermediate hosts, and the African giant snail Achatina fulica is considered one of the most important around the world. Experimental data concerning A. cantonensis infection in the African giant snail remains notably limited. This helminth causes eosinophilic meningitis or meningoencephalitis in humans, representing an emergent zoonosis in Brazil. Understanding the host-parasite relationship through the application of new tools is crucial, given the complex interaction between zoonosis and the intricate mechanisms involving wild/human hosts, parasite adaptation, and dispersion. The objective of this study was to employ SEM as a novel methodology to understand the structural organization of the host tissue, particularly the granuloma formation. This sheds light on the complex balance between A. fulica and A. cantonensis. Nine three-month-old snails were randomly selected and exposed for 24 h to a concentration of 2000 L1/dose of A. cantonensis. A necropsy was performed 37 days after the infection, and the samples were examined using light and scanning electron microscopy (SEM). The histopathological results revealed third-stage larvae of A. cantonensis associated with granulomas distributed throughout the head-foot mass, mantle, and kidney. Scanning electron microscopy of the histological section surface showed that the granuloma is surrounded by a cluster of spherical particles, which are distributed in the region bordering the larvae. This reveal details of the nematode structure, demonstrating how this methodology can enhance our understanding of the role of granulomas in molluscan tissue. The structural characteristics of granuloma formation in A. fulica suggest it as an excellent invertebrate host for A. cantonensis. This relationship appears to provide protection to the parasite against the host's immune defense system while isolating the snail's tissue from potential exposure to nematode antigens.

External Parasites of Fish: A Comprehensive Overview

Fishes are a diverse group of gill-bearing aquatic craniate animals characterized by their limbless bodies. These creatures are susceptible to various diseases, both infectious and non-infectious, which can significantly impact fish populations. One critical factor contributing to reduced fish productivity is parasitic infestation. This paper aims to provide a comprehensive overview of the external parasites that affect fish. In aquatic environments, host-parasite interactions are complex, with crustacean parasites often playing a prominent role in fish diseases and the management of captive and cultured fish stocks. Among the most common crustacean parasites of fish, we find copepods, brachiura, and isopods. Copepods, for example, encompass two major crab families: Ergasilidae and Lernaeidae. In contrast, Branchiura (Argulidae) and Isopoda members, both parasitic, generally exhibit larger body sizes than copepods. While these parasites may cause only mild harm to their hosts when present in small quantities, copepods are the most prevalent crustacean parasites in various aquatic habitats, including freshwater, brackish water, and saltwater. In the context of fish health and productivity, prevention often proves more effective than treatment. Implementing strategies such as strict controls when introducing new fish to a newly established tank, robust quarantine procedures, mechanical removal using forceps, freshwater or saltwater dips, and water treatments involving organophosphates can significantly reduce the incidence of external parasite infestations. Therefore, exercising caution when introducing new fish into a population is essential.

Classifying tetraspanins: A universal system for numbering residues and a proposal for naming structural motifs and subfamilies

All tetraspanins have four transmembrane domains (TMs). The large extracellular loop (LEL) that connects the third and fourth TMs contains multiple secondary structures together with the family's signature Cys-Cys-Gly motif. These intriguing membrane proteins are involved in diverse and incompletely understood cellular processes including cell adhesion, tissue differentiation, immune cell maturation and host-parasite interactions. Here we present a classification system that accurately describes the position of each amino acid within its primary sequence based on both sequence and topological conservation of the TMs and LEL. This builds on the numbering systems that have been used in the G protein-coupled receptor (GPCR) field for nearly three decades and which have aided the understanding of GPCR structure/activity relationships and ligand interactions. The high-resolution structures of the tetraspanins CD81, CD9, CD53 and Tspan15 were used to validate the structural relevance of our new tetraspanin classification system. Modelling of all tetraspanin LELs highlighted flexibility in LEL disulfide bonding across the family and suggests that the structural arrangement of tetraspanin LELs is more complex than previously thought. We therefore propose a new subfamily naming system that addresses this added complexity and facilitates the systematic classification of human tetraspanins, shedding light on all structural motifs within the family. We anticipate that our universal tetraspanin classification system will enable progress in defining how sequence and structure inform function.

PIP2 regulating calcium signal modulates actin cytoskeleton-dependent cytoadherence and cytolytic capacity in the protozoan parasite Trichomonas vaginalis.

Trichomonas vaginalis is a prevalent causative agent that causes trichomoniasis leading to uropathogenic inflammation in the host. The crucial role of the actin cytoskeleton in T. vaginalis cytoadherence has been established but the associated signaling has not been fully elucidated. The present study revealed that the T. vaginalis second messenger PIP2 is located in the recurrent flagellum of the less adherent isolate and is more abundant around the cell membrane of the adherent isolates. The T. vaginalis phosphatidylinositol-4-phosphate 5-kinase (TvPI4P5K) with conserved activity phosphorylating PI(4)P to PI(4, 5)P2 was highly expressed in the adherent isolate and partially colocalized with PIP2 on the plasma membrane but with discrete punctate signals in the cytoplasm. Plasma membrane PIP2 degradation by phospholipase C (PLC)-dependent pathway concomitant with increasing intracellular calcium during flagellate-amoeboid morphogenesis. This could be inhibited by Edelfosine or BAPTA simultaneously repressing parasite actin assembly, morphogenesis, and cytoadherence with inhibitory effects similar to the iron-depleted parasite, supporting the significance of PIP2 and iron in T. vaginalis colonization. Intriguingly, iron is required for the optimal expression and cell membrane trafficking of TvPI4P5K for in situ PIP2 production, which was diminished in the iron-depleted parasites. TvPI4P5K-mediated PIP2 signaling may coordinate with iron to modulate T. vaginalis contact-dependent cytolysis to influence host cell viability. These observations provide novel insights into T. vaginalis cytopathogenesis during the host-parasite interaction.

Reproduction of Varroa destructor depends on well-timed host cell recapping and seasonal patterns

Resistance traits of honeybees (Apis mellifera) against their major parasite Varroa destructor have fascinated scientists and breeders for long. Nevertheless, the mechanisms underlying resistance are still largely unknown. The same applies to possible interactions between host behaviours, mite reproduction and seasonal differences. Two resistance traits, reproductive failure of mites and recapping of brood cells, are of particular interest. High rates of recapping at the colony level were found to correspond with low reproductive success of mites. However, the direct effect of recapping on mite reproduction is still controversial and both traits seem to be very variable in their expression. Thus, a deeper knowledge of both, the effect of recapping on mite reproduction and the seasonal differences in the expression of these traits is urgently needed. To shed light on this host-parasite interaction, we investigated recapping and mite reproduction in full-grown colonies naturally infested with V. destructor. Measurements were repeated five times per year over the course of 3 years. The reproductive success of mites as well as the recapping frequency clearly followed seasonal patterns. Thereby, reproductive failure of mites at the cell level was constantly increased in case of recapping. Interestingly, this did not apply to the occurrence of infertile mites. In line with this, recapping activity in fertile cells was most frequent in brood ages in which mite offspring would be expected. Our results suggest that mite offspring is the main target of recapping. This, in turn, leads to a significantly reduced reproductive success of the parasite.

Amyloodiniosis in aquaculture: A review

AbstractFish ectoparasites are one of the pathogens groups that pose great concern to the aquaculture industry. The dinoflagellate Amyloodinium ocellatum is responsible for amyloodiniosis, a parasitological disease with a strong economic impact in temperate and warm water aquaculture, mainly in earthen pond semi‐intensive systems. Amyloodiniosis represents one of the most important bottlenecks for aquaculture and, with the predictable expansion of the area of influence of this parasite to higher latitudes due to global warming it might also be a threat to other aquaculture species that are not yet parasitized by A. ocellatum. This review made a compilation of the existing knowledge about this parasite and the disease associated with it. It was noticed that, except from the life cycle characterisation, detection methods, histopathological analysis, and treatments, there are still a lot of areas that need a further investment in research. Areas like parasite–host interactions, epidemiological models, taxonomy, host physiological responses to parasitism, and genome sequencing, amongst others, can contribute to a better understanding of this disease. These proposed approaches and routes of investigation will enhance and contribute to a more standardised knowledge, creating the opportunity for a better understanding of amyloodiniosis impacts on fish and contributing for the development of new tools against A. ocellatum, that may reduce fish mortality in aquaculture production due to amyloodiniosis outbreaks.

Climate heterogeneity, season variation, and sexual dimorphism modulate the association between MHC II diversity and parasite variation in striped hamster.

Parasite-mediated selection is widely believed to play a crucial role in maintaining the diversity of the major histocompatibility complex (MHC) genes, which is thought to be maintained through heterozygote advantage, rare-allele advantage, and fluctuating selection. However, the relationship between parasite pressure and MHC diversity has yielded inconsistent findings. These inconsistencies may arise from the influence of environmental factors and individual variations in traits on host-parasite interactions. To address these issues, our study extensively investigated populations of striped hamsters inhabiting regions characterized by environmental heterogeneity. The primary objective was to examine the universality of parasite-mediated selection mechanisms. Our observations revealed the presence of multiple parasite infections, accompanied by spatial and temporal variations in parasite communities and infection patterns among individual hamsters. Specifically, the temperature was found to influence all four parasite indices, while the presence of gamasid mites and parasite richness decreased with increasing precipitation. We also noted significant seasonal variation in parasite dynamics. Moreover, a significant sexual dimorphism was observed with males exhibiting a considerably higher parasite burden compared to their female counterparts. Lastly, we identified the maintenance of MHC polymorphism in striped hamsters as being driven by the heterozygote advantage and fluctuating selection mechanisms. This study underscores the significance of ecological processes in comprehending host-parasite systems and highlights the necessity of considering environmental factors and individual traits when elucidating the mechanisms underlying MHC diversity mediated by parasites.

Fasciolosis: pathogenesis, host-parasite interactions, and implication in vaccine development.

Fasciola hepatica is distributed worldwide, causing substantial economic losses in the animal husbandry industry. Human fasciolosis is an emerging zoonosis in Andean America, Asia, and Africa. The control of the disease, both in humans and animals, is based on using anthelmintic drugs, which has resulted in increased resistance to the most effective anthelmintics, such as triclabendazole, in many countries. This, together with the concerns about drug residues in food and the environment, has increased the interest in preventive measures such as a vaccine to help control the disease in endemic areas. Despite important efforts over the past two decades and the work carried out with numerous vaccine candidates, none of them has demonstrated consistent and reproducible protection in target species. This is at least in part due to the high immunomodulation capacity of the parasite, making ineffective the host response in susceptible species such as ruminants. It is widely accepted that a deeper knowledge of the host-parasite interactions is needed for a more rational design of vaccine candidates. In recent years, the use of emerging technologies has notably increased the amount of data about these interactions. In the present study, current knowledge of host-parasite interactions and their implication in Fasciola hepatica vaccine development is reviewed.

Identification of a non-exported Plasmepsin V substrate that functions in the parasitophorous vacuole of malaria parasites.

In the manuscript, the authors investigate the role of the protease Plasmepsin V in the parasite-host interaction. Whereas processing by Plasmepsin V was previously thought to target a protein for export into the host cell, the authors now show that there are proteins cleaved by this protease that are not exported but instead function at the host-parasite interface. This changes the view of this protease, which turns out to have a much broader role than anticipated. The result shows that the protease may have a function much more similar to that of related organisms. The authors also investigate the requirements for protein export by analyzing exported and non-exported proteins and find commonalities between the proteins of each set that further our understanding of the requirements for protein export.

Seasonal and spatial patterns of infestation with ectoparasitic mites on New Zealand geckos revealed using a crowd‐sourced citizen science database

AbstractThe advent of online crowd‐sourced nature databases provides an opportunity to yield information about ecological interactions on a scale not previously possible. In particular, such databases provide an opportunity to collate information on host–parasite interactions through screening photographs of hosts. Using photographs from iNaturalist we expanded the known hosts for ectoparasitic mites in New Zealand geckos from 9 to 20 host species, including the first report of ectoparasitic mites on geckos from the genus Toropuku. Additionally, spatial and seasonal variation in mite prevalence was investigated, giving deeper insight in the possibilities of analysing crowd‐sourced datasets.

Host-parasite interactions: a study on the pathogenicity of different Mesanophrys sp. densities and hemocytes-mediated parasitic resistance of swimming crabs (Portunus trituberculatus).

Mesanophrys sp. is a parasitic ciliate that invades and destroys the hemocytes of the swimming crab (Portunus trituberculatus). In the present study, we employed an in vitro model to elucidate how Mesanophrys sp. destroys crab hemocytes. We also evaluated the relationship between the parasite's density, the destruction rate of the hemocytes, and the rapid proliferation pattern of parasites in host crabs. We found that the survival rate and cell integrity of crab hemocytes decreased with an increase in Mesanophrys sp. density, depicting a negative correlation between hemocyte viability and parasite density. Further analyses revealed that crab hemocytes could resist destruction by a low density (10 ind/mL) of Mesanophrys sp. for a long time (60h). Mesanophrys sp. and its culture medium (containing the ciliate secretions) destroy the host hemocytes. The natural population growth rate of Mesanophrys sp. decreased with an increase in the parasite density, but the Mesanophrys sp. density did not affect the generation time of the parasites. In summary, Mesanophrys sp. can destroy crab hemocytes, and the degree of destruction is directly proportional to the parasite density. The resistance of crab hemocytes to Mesanophrys sp. decreased gradually with an increase in the parasite density.

Comparative analysis of peripheral whole blood transcriptome from asymptomatic carriers reveals upregulation of subsets of surface proteins implicated in Plasmodium falciparum phenotypic plasticity

The molecular mechanism underlying Plasmodium falciparum's persistence in the asymptomatic phase of infection remains largely unknown. However, large-scale shifts in the parasites' gene expression during asymptomatic infections may enhance phenotypic plasticity, maximizing their fitness and leading to the persistence of the asymptomatic infections. To uncover these mechanisms, we aimed to identify parasite genetic factors implicated in asymptomatic infections through whole transcriptome analysis. We analyzed publicly available transcriptome datasets containing asymptomatic malaria (ASM), uncomplicated malaria (SM), and malaria-naïve (NSM) samples from 35 subjects for differentially expressed genes (DEGs) and long noncoding RNAs. Our analysis identified 755 and 1773 DEGs in ASM vs SM and NSM, respectively. These DEGs revealed sets of genes coding for proteins of unknown functions (PUFs) upregulated in ASM vs SM and ASM, suggesting their role in underlying fundamental molecular mechanisms during asymptomatic infections. Upregulated genes in ASM vs SM revealed a subset of 24 clonal variant genes (CVGs) involved in host-parasite and symbiotic interactions and modulation of the symbiont of host erythrocyte aggregation pathways. Moreover, we identified 237 differentially expressed noncoding RNAs in ASM vs SM, of which 11 were found to interact with CVGs, suggesting their possible role in regulating the expression of CVGs. Our results suggest that P. falciparum utilizes phenotypic plasticity as an adaptive mechanism during asymptomatic infections by upregulating clonal variant genes, with long noncoding RNAs possibly playing a crucial role in their regulation. Thus, our study provides insights into the parasites' genetic factors that confer a fitness advantage during asymptomatic infections.