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Schistosoma mansoni infection is associated with hepatic inflammation and fibrosis, but its systemic metabolic effects remain poorly understood. This study aimed to investigate changes in the serum lipidomic profile associated with S. mansoni infection and parasite load in individuals from an endemic area. This cross-sectional analysis was nested within a longitudinal cohort study conducted in northeastern Brazil. Parasitological diagnosis and quantification were performed using the Kato–Katz technique. A total of 45 individuals were selected and divided into three groups: high parasite load (HL), low parasite load (LL), and uninfected controls (NegE). Serum samples were analyzed using mass-spectrometry-based lipidomics. The most abundant lipid subclasses across all groups were phosphatidylcholines (PC), triacylglycerols (TAG), and phosphatidylethanolamines (PE). However, individuals in the HL group exhibited distinct lipidomic profiles, with increased levels of specific phosphatidylinositols (PI) and reduced levels of certain TAG species compared to the NegE group. These changes may reflect host–parasite interactions and immune–metabolic alterations driven by intense infection. Our findings suggest that S. mansoni infection, particularly at higher parasite burdens, can influence the host’s serum lipid profile and may contribute to metabolic disturbances in endemic populations.

Background Despite decades of research, an effective schistosomiasis vaccine remains elusive. The radiation-attenuated (RA) cercarial vaccine remains the best model for eliciting high levels of protection. We have recently explored this model in mice to identify potentially protective pathways by examining gene expression patterns in peripheral blood mononuclear cells (PBMC). Methods Herein, we reanalyzed the transcriptomic data from PBMC obtained from vaccinated and infected C57BL/6 mice in three timepoints (Days 7 and 17 after infection or vaccination and Day 7 post-challenge). In addition, we generated new data on PBMC collected 35 days after infection. Deconvolution analysis was performed to estimate immune cell composition by CIBERSORTx. Gene co-expression networks and over-representation analysis (ORA) were performed using the CEMiTool package. Protein-protein interaction networks were constructed using STRING, and the hub proteins for each module were identified using Cytoscape. Results Co-expression network analysis identified a module (M2) associated with the infection process, grouping genes related to a Th2 immune response, and a second module (M6) associated with the vaccination process, displaying pathways related to a Th1 response, CD8 + T cells and NK cells. Within each module, five hub proteins were identified based on protein-protein interaction networks. The M2 infection module revealed Chil3, Il4, Cx3cr1, Emr1 and Ccl2 as hubs, while module M6, associated with vaccination, disclosed Prf1, Klrc1, IFN-γ, Ncr1 and Tbx21 as hub proteins. Conclusions Our data point to the potentiald role of NK cells that may contribute to the RA vaccine response through the production of IFN-γ orchestrated by the T-bet transcription factor (Tbx21). Graphical Abstract

The self-cure of rhesus macaques from a schistosome infection and their subsequent strong immunity to a cercarial challenge should provide novel insights into the way these parasites can be eliminated by immunological attack. High-density arrays comprising overlapping 15-mer peptides from target proteins printed on glass slides can be used to screen sera from host species to determine antibody reactivity at the single epitope level. Careful selection of proteins, based on compositional studies, is crucial to encompass only those exposed on or secreted from the intra-mammalian stages and is intended to focus the analysis solely on targets mediating protection. We report the results of this approach using two pools of sera from hi- and lo-responder macaques undergoing self-cure, to screen arrays comprising tegument, esophageal gland, and gastrodermis proteins. We show that, overall, the target epitopes are the same in both groups, but the intensity of response is twice as strong in the high responders. In addition, apart from Sm25, tegument proteins elicit much weaker responses than those originating in the alimentary tract, as was apparent in IFNγR KO mice. We also highlight the most reactive epitopes in key proteins. Armed with this knowledge, we intend to use multi-epitope constructs in vaccination experiments, which seek to emulate the self-cure process in experimental animals and potentially in humans.

On the surface of the promastigote, phosphoglycans (PG) such as lipophosphoglycan (LPG), proteophosphoglycan (PPG), free phosphoglycan polymers (PGs), and acid phosphatases (sAP), are dominant and contribute to the invasion and survival of within the host cell by modulating macrophage signaling and intracellular trafficking. Phosphoglycan synthesis depends on the Golgi GDP-mannose transporter encoded by the gene. Aiming to investigate the role of PG-containing molecules in infection process, herein we describe the generation and characterization of -deficient parasites. This gene was unexpectedly identified as duplicated in the genome, which impaired gene targeting using the conventional homologous recombination approach. This limitation was circumvented by the use of CRISPR/Cas9 technology. Knockout parasites were selected by agglutination assays using CA7AE antibodies followed by a lectin (RCA 120). Five clones were isolated and molecularly characterized, all revealing the expected edited genome, as well as the complete absence of LPG and PG-containing molecule expression. Finally, the deletion of was found to impair the outcome of infection in human neutrophils, as demonstrated by a pronounced reduction (~83%) in intracellular load compared to wild-type parasite infection. The results obtained herein reinforce the importance of LPG and other PGs as virulence factors in host-parasite interactions.

Background Schistosoma mansoni venom allergen-like protein (SmVAL) is a gene family composed of 29 members divided into group 1 encoding proteins potentially secreted, and group 2 encoding intracellular components. Some members were found to be upregulated in the transition of germ ball - cercariae - day 3 schistosomula, suggesting that group 1 SmVAL proteins are associated with the invasion of the human host, although their functions are not completely established. Recently, we have described the localization of SmVAL7 (group 1) and SmVAL6 (group 2) transcripts in the oesophageal gland and in the oral and ventral suckers of adult parasites, respectively. The expression patterns of the two genes suggest that SmVAL7 protein plays a role in the blood-feeding process while SmVAL6 is associated with the parasite attachment and movement in the vasculature. In this way, searching for additional secreted SmVAL proteins that could be involved in key processes from skin penetration to the beginning of blood-feeding, we investigated the tissue localization of SmVAL4, 13, 16 and 24 by whole-mount in situ hybridization (WISH). Results We report here the localization of group 1 SmVAL4 and 24 transcripts in the pre-acetabular glands of developing germ balls. Time course experiments of in vitro cultured schistosomula after cercariae transformation demonstrated that SmVAL4 protein is secreted during the first 3 h of in vitro culture, correlating with the emptying of acetabular glands as documented by confocal microscopy. In addition, the localization of SmVAL13 transcripts in adult male anterior oesophageal gland suggests that the respective protein may be involved in the first steps of the blood-feeding process. SmVAL16 was localized close to the neural ganglia and requires further investigation. Conclusions Our findings demonstrate that SmVAL proteins have localizations that place them in strategic positions to be considered as potential vaccine candidates as some members are exposed to interaction with the immune system and may participate in key processes of mammalian invasion and parasitism establishment.

The Schistosoma mansoni Venom-Allergen-Like proteins (SmVALs) are members of the SCP/TAPS (Sperm-coating protein/Tpx-1/Ag5/PR-1/Sc7) protein superfamily, which may be important in the host-pathogen interaction. Some of these molecules were suggested by us and others as potential immunomodulators and vaccine candidates, due to their functional classification, expression profile and predicted localization. From a vaccine perspective, one of the concerns is the potential allergic effect of these molecules. Herein, we characterized the putative secreted proteins SmVAL4 and SmVAL26 and explored the mouse model of airway inflammation to investigate their potential allergenic properties. The respective recombinant proteins were obtained in the Pichia pastoris system and the purified proteins used to produce specific antibodies. SmVAL4 protein was revealed to be present only in the cercarial stage, increasing from 0-6 h in the secretions of newly transformed schistosomulum. SmVAL26 was identified only in the egg stage, mainly in the hatched eggs' fluid and also in the secretions of cultured eggs. Concerning the investigation of the allergic properties of these proteins in the mouse model of airway inflammation, SmVAL4 induced a significant increase in total cells in the bronchoalveolar lavage fluid, mostly due to an increase in eosinophils and macrophages, which correlated with increases in IgG1, IgE and IL-5, characterizing a typical allergic airway inflammation response. High titers of anaphylactic IgG1 were revealed by the Passive Cutaneous Anaphylactic (PCA) hypersensitivity assay. Additionally, in a more conventional protocol of immunization for vaccine trials, rSmVAL4 still induced high levels of IgG1 and IgE. Our results suggest that members of the SmVAL family do present allergic properties; however, this varies significantly and therefore should be considered in the design of a schistosomiasis vaccine. Additionally, the murine model of airway inflammation proved to be useful in the investigation of allergic properties of potential vaccine candidates.

Innate immune cells such as monocytes and macrophages are activated in response to microbial and other challenges and mount an inflammatory defensive response. Exposed cells develop the so-called innate memory, which allows them to react differently to a subsequent challenge, aiming at better protection. In this study, using human primary monocytes in vitro, we have assessed the memory-inducing capacity of two antigenic molecules of Schistosoma mansoni in soluble form compared to the same molecules coupled to outer membrane vesicles of Neisseria lactamica. The results show that particulate challenges are much more efficient than soluble molecules in inducing innate memory, which is measured as the production of inflammatory and anti-inflammatory cytokines (TNFα, IL-6, IL-10). Controls run with LPS from Klebsiella pneumoniae compared to the whole bacteria show that while LPS alone has strong memory-inducing capacity, the entire bacteria are more efficient. These data suggest that microbial antigens that are unable to induce innate immune activation can nevertheless participate in innate activation and memory when in a particulate form, which is a notion that supports the use of nanoparticulate antigens in vaccination strategies for achieving adjuvant-like effects of innate activation as well as priming for improved reactivity to future challenges.

The Arabidopsis thaliana THI1 protein is involved in thiamine biosynthesis and is targeted to both chloroplasts and mitochondria by N-terminal control regions. To investigate thi1 expression, a series of thi1 promoter deletions were fused to the β-glucuronidase (GUS) reporter gene. Transgenic plants were generated and expression patterns obtained under different environmental conditions. The results show that expression derived from the thi1 promoter is detected early on during development and continues throughout the plant's life cycle. High levels of GUS expression are observed in both shoots and roots during vegetative growth although, in roots, expression is restricted to the vascular system. Deletion analysis of the thi1 promoter region identified a region that is responsive to light. The smallest fragment (designated Pthi322) encompasses 306 bp and possesses all the essential signals for tissue specificity, as well as responsiveness to stress conditions such as sugar deprivation, high salinity, and hypoxia.

Background The Schistosoma mansoni Venom-Allergen-Like proteins (SmVALs) are members of the SCP/TAPS (Sperm-coating protein/Tpx-1/Ag5/PR-1/Sc7) protein superfamily, which may be important in the host-pathogen interaction. Some of these molecules were suggested by us and others as potential immunomodulators and vaccine candidates, due to their functional classification, expression profile and predicted localization. From a vaccine perspective, one of the concerns is the potential allergic effect of these molecules. Methodology/Principal Findings Herein, we characterized the putative secreted proteins SmVAL4 and SmVAL26 and explored the mouse model of airway inflammation to investigate their potential allergenic properties. The respective recombinant proteins were obtained in the Pichia pastoris system and the purified proteins used to produce specific antibodies. SmVAL4 protein was revealed to be present only in the cercarial stage, increasing from 0-6 h in the secretions of newly transformed schistosomulum. SmVAL26 was identified only in the egg stage, mainly in the hatched eggs' fluid and also in the secretions of cultured eggs. Concerning the investigation of the allergic properties of these proteins in the mouse model of airway inflammation, SmVAL4 induced a significant increase in total cells in the bronchoalveolar lavage fluid, mostly due to an increase in eosinophils and macrophages, which correlated with increases in IgG1, IgE and IL-5, characterizing a typical allergic airway inflammation response. High titers of anaphylactic IgG1 were revealed by the Passive Cutaneous Anaphylactic (PCA) hypersensitivity assay. Additionally, in a more conventional protocol of immunization for vaccine trials, rSmVAL4 still induced high levels of IgG1 and IgE. Conclusions Our results suggest that members of the SmVAL family do present allergic properties; however, this varies significantly and therefore should be considered in the design of a schistosomiasis vaccine. Additionally, the murine model of airway inflammation proved to be useful in the investigation of allergic properties of potential vaccine candidates.

The Aspergillus genus, the etiological agent of aspergillosis, is an important food contaminant and mycotoxin producer. Plant extracts and essential oils are a source of bioactive substances with antimicrobial potential that can be used instead of synthetic food preservatives. Species from the Lauraceae family and the Ocotea genus have been used as traditional medicinal herbs. Their essential oils can be nanoemulsified to enhance their stability and bioavailability and increase their use. Therefore, this study sought to prepare and characterize both nanoemulsion and essential oil from the Ocotea indecora’s leaves, a native and endemic species from the Mata Atlântica forest in Brazil, and evaluate the activity against Aspergillus flavus RC 2054, Aspergillus parasiticus NRRL 2999, and Aspergillus westerdjikiae NRRL 3174. The products were added to Sabouraud Dextrose Agar at concentrations of 256, 512, 1024, 2048, and 4096 µg/mL. The strains were inoculated and incubated for up to 96 h with two daily measurements. The results did not show fungicidal activity under these conditions. A fungistatic effect, however, was observed. The nanoemulsion decreased the fungistatic concentration of the essential oil more than ten times, mainly in A. westerdjikiae. There were no significant changes in aflatoxin production.