Parasite Immunology最新文献

{"title":"Hepatic Granulomatous Inflammation and Angiogenesis Upregulation Provoked by Acanthamoeba polyphaga Infection and Role of Quercetin-Conjugated Silver Nanoparticles.","authors":"Yousef Abdal Jalil Fadladdin, Mahmoud Abdel-Zaher Abdel-Samiee, Mona Mohamed Ali Khalaf, Gamal Hassan Abed, Nancy K Ramadan, Sally Salah Abdel-Hakeem, Sara Salah Abdel-Hakeem","doi":"10.1111/pim.70098","DOIUrl":"https://doi.org/10.1111/pim.70098","url":null,"abstract":"<p><p>Disseminated acanthamoebiasis is a rare but severe opportunistic infection that can involve multiple organs, including the liver, causing fatal outcomes. This study provides new insights into hepatic pathogenesis and possible relationship with angiogenesis activity and the therapeutic role of quercetin conjugated silver nanoparticles (Q-AgNPs). Sixty BALB/c mice were divided into four groups: uninfected control, uninfected treated with Q-AgNPs, infected group and infected treated with Q-AgNPs. The Q-AgNPs were synthesised and characterised by spectrophotometry, electron microscope, zeta potential and dynamic light scattering. Hepatic tissues were examined histopathologically for granulomas (classified as caseating/non-caseating and immature/mature) and vascular changes. Hypoglycaemia and expression of angiogenic markers (CD31, CD34 and MMP9) were assessed. Acanthamoeba polyphaga infection induced significant hepatic granulomatous inflammation, hypoglycaemia, vascular remodelling and upregulation of CD31, CD34 and MMP9, indicating active angiogenesis. Granulomas exhibited necrotic cores in some cases and progressed from immature to mature stages. Q-AgNPs treatment markedly attenuated granuloma numbers, suppressing angiogenic marker expression, mitigating inflammation, capillary permeability and liver lesions. This study provides novel evidence linking Acanthamoeba infection to hepatic granuloma formation and angiogenesis-driven pathology which may serve as useful biomarkers for extracerebral acanthamoebiasis. Further studies are needed to evaluate long-term outcomes and host-parasite interaction.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 9","pages":"e70098"},"PeriodicalIF":1.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of the CD47-SIRPα Axis Causes Profound Reduction of Parasitaemia in Mice Infected With Babesia microti.","authors":"Shamim Mohammad, Ioana Brasov, Susan Gottshall, Sarah Robins, Sujatha Rashid, Rebecca Bradford, Robert E Molestina","doi":"10.1111/pim.70099","DOIUrl":"10.1111/pim.70099","url":null,"abstract":"<p><p>Human babesiosis is an emerging disease in North America caused by the red blood cell (RBC)-infecting parasite Babesia microti. Despite a rise in clinical cases in recent years, the pathogenesis and host immune response to B. microti infection remain unclear. CD47 is a 'marker of self' transmembrane glycoprotein expressed on cell membranes that inhibits phagocytosis through interactions with macrophage signal-regulatory protein alpha (SIRPα). We posit that disruption of CD47-SIRPα signalling will induce macrophage uptake of Babesia-infected RBCs and reduce parasitaemia in susceptible hosts. To evaluate this, we compared the in vivo clearance of B. microti in CD47 knockout (CD47^-/-) mice and wild-type C57BL/6J mice. Our results showed pronounced differences in infection kinetics between the two mouse strains. C57BL/6J mice showed steadily increasing parasitaemia that peaked at an average of 12%, whereas CD47^-/- mice exhibited parasitaemia that never exceeded 1.5% throughout infection. Parasitaemia became undetectable by Day 21 in C57BL/6J and by Day 16 in CD47^-/- mice, indicating resolution of infection. These results imply that, in the absence of CD47, growth of B. microti is diminished due to more efficient phagocytosis of infected RBCs by macrophages. We propose that CD47-SIRPα signalling plays a key role in the innate response to Babesia and suggest CD47 modulation as a new therapeutic target for the treatment of babesiosis.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 8","pages":"e70099"},"PeriodicalIF":1.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13447032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attenuation of Tau Hyperphosphorylation by Chronic Toxoplasma gondii Infection in a Mouse Model of Alzheimer's Disease.","authors":"Seung-Hwan Seo, Ji-Eun Lee, Eun-Ji Cho, Eun-Hee Shin","doi":"10.1111/pim.70096","DOIUrl":"10.1111/pim.70096","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) peptide accumulation and tau protein-mediated neurodegeneration, and neuroinflammation is increasingly recognized as a major process associated with tau pathology. Chronic Toxoplasma gondii infection reduces amyloid accumulation in AD models through immune modulation, but its stage-specific associations with tau-related pathology remain unclear. Here, we investigated how chronic T. gondii infection is associated with tau-related molecular and neuropathological changes in the 5XFAD AD mouse model. At 40 weeks post-infection, we profiled transcriptomic changes and evaluated Aβ-associated (21 genes), Aβ/tau-shared (22 genes), and tau-associated (21 genes) pathological programs together with p-tau immunoreactivity in brain sections. Chronic infection was associated with selective modulation of molecular networks linked to neuroimmune signalling and tau-related pathways rather than broad suppression of AD-related gene expression. Among tau-related pathological stages, the neuroinflammation-related amplification module linking Aβ and tau exhibited the most prominent transcriptomic change in T. gondii-infected AD mice, whereas upstream kinase-related initiation pathways and downstream toxin conversion or accumulation-related processes changed relatively minimally. These transcriptomic changes were accompanied by a marked reduction in phosphorylated tau load at the tissue level. Collectively, these findings suggest that chronic T. gondii infection is associated with selective modulation of tau-related pathogenic programs and reduced p-tau burden in the 5XFAD brain.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 8","pages":"e70096"},"PeriodicalIF":1.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13459155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxic CD4⁺ T Cells in Visceral Leishmaniasis Patients.","authors":"Shashi Bhushan Chauhan, Siddharth Sankar Singh, Bhawana Singh, Shashi Kumar, Rahul Tiwari, Vibhav Gautam, Fabian Rivera, Susanne Nylen, Christian Engwerda, Shyam Sundar, Rajiv Kumar","doi":"10.1111/pim.70097","DOIUrl":"https://doi.org/10.1111/pim.70097","url":null,"abstract":"<p><p>Visceral leishmaniasis (VL), a parasitic disease caused by Leishmania donovani, requires a robust CD4⁺ T-cells response to control parasite replication by interferon-gamma (IFN-γ) production and activation of macrophages. However, in VL patients, the anti-parasitic CD4⁺ T-cell responses are ineffective for reasons that are still unclear. Our recent study reporting a transcriptional signature of CD4⁺ T-cell isolated from the peripheral blood of active VL patients showed enhanced expression of genes related to cytotoxicity. This study investigates the cytotoxic potential of CD4⁺ T-cells in VL patients, focusing on the expression of the key cytotoxic molecules granzyme B (GZMB), granulysin (GNLY), perforin (PRF), natural killer cell granule protein 7 (NKG7) and the degranulation capacity of CD4⁺ T-cells during infection. We observed significant upregulation of these cytotoxic markers in CD4⁺ T-cells from VL patients, particularly prior to anti-parasitic drug treatment (D0), suggesting activation of these cells. However, the degranulation capacity, as indicated by CD107a expression, was comparable between VL patients and endemic controls (ECs), suggesting potential functional impairment in the cytotoxic response. Yet, antigen-specific GZMB secretion in whole blood cultures and intracellular GZMB production in CD4⁺ T-cell subsets (notably Th1, Th9 and Th17/22 cells) were enhanced in VL patients, indicating a robust antigen-specific response, though this did not translate into effective parasite control. These findings highlight a paradox whereby CD4⁺ T-cells from VL patients have heightened production of cytotoxic molecules, but lack translocation of CD107a to the cell surface, which is associated with an inability to eliminate parasites. This study provides new insights into the immune dysfunction in VL, highlighting a potential role for the cytotoxic phenotype that develops in parasite-specific CD4⁺ T-cells. Targeting these pathways may offer novel therapeutic strategies to enhance immune responses and improve clinical outcomes in VL.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 8","pages":"e70097"},"PeriodicalIF":1.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13482423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Could Fluoxetine Confer a Favourable Immuno-Inflammatory Profile in a Murine Model of Acute Toxoplasmosis?","authors":"Wesam M A Elgendy, Ahmad A Othman, Basma N Khalifa, Nema A Soliman, Dareen Mohamed, Salwa S Younis","doi":"10.1111/pim.70093","DOIUrl":"https://doi.org/10.1111/pim.70093","url":null,"abstract":"<p><p>Acute toxoplasmosis could be life-threatening, as the body is overwhelmed both by the rapidly replicating tachyzoites and the immunopathological sequelae of the robust immune response with no satisfactory treatment or vaccine available to date. Fluoxetine, a selective serotonin reuptake inhibitor, is recently repurposed to control cytokine storm in certain clinical settings. In this study, an animal model of acute toxoplasmosis was established using the virulent RH strain. To compare their therapeutic effects, either spiramycin or fluoxetine was administered for 5 days starting from the day of infection. To assess its prophylactic effects, fluoxetine was started 2 weeks before induction of the infection. It was found that fluoxetine as well as spiramycin achieved comparable reduction of the tachyzoite counts with prominent deleterious morphological effects on the tachyzoites detected by scanning electron microscopy. Both drugs improved the histopathological changes with superior effect of fluoxetine, particularly in the brain. Fluoxetine attenuated substantially the inflammatory response through the reduction of TNF-α, IL-4 and MCP-1 levels. Prophylactic fluoxetine administration also induced improvement of the redox status. Moreover, fluoxetine exhibited superior effect in reversal of infection-induced modulation of apoptosis and vascular dysfunction in the brain via significantly reducing the levels of p21 and endocan, respectively. Fluoxetine also upregulated the levels of growth differentiation factor 15 in the spleen, partly accounting for the limitation of the immunopathology. In conclusion, fluoxetine showed antiparasitic activity comparable to that of spiramycin, and displayed superior anti-inflammatory, immunomodulatory, vascular protective and pro-apoptotic effects, leading to better survival in acute murine toxoplasmosis.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 7","pages":"e70093"},"PeriodicalIF":1.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of Splenic CD8αβ⁺ γδT Cells in Plasmodium yoelii Infection.","authors":"Xingfei Pan, Li Pan, Xingyue Wang, Meiling Liu, Haiwen Yuan, Mingjie Chen, Xiongyu Xie, Qi Ye, Lixin Luo, Guikuan Liang, Hongyan Xie, Jun Huang","doi":"10.1111/pim.70091","DOIUrl":"10.1111/pim.70091","url":null,"abstract":"<p><p>γδT cells are a subset of innate lymphocytes that play an essential role in anti-infection immunity. However, the functional role of CD8αβ⁺ γδT cells, a distinct subset of γδT cells, remains poorly characterized during malaria infection. Female C57BL/6 mice were intraperitoneally injected with 1 × 10⁶ Plasmodium yoelii-infected red blood cells (iRBCs). At 12 days post-infection (12 dpi, the peak of parasitemia), spleens were harvested and lymphocytes were isolated. Fluorescence-activated cell sorting (FACS) was performed to determine the frequency, phenotypic features and functional properties of CD8αβ⁺ γδT cells. Meanwhile, CD45⁺ lymphocytes were sorted for single-cell RNA sequencing (scRNA-seq) to compare differentially expressed genes between CD8αβ⁺ γδT and CD8αα⁺ γδT cell subsets. FACS analysis revealed a significant increase in CD8αβ⁺ γδT cells following P. yoelii infection. These cells exhibited elevated expression of activation-related molecules, enhanced effector functions, preferential polarization towards an IFN-γ-producing (γδT1) phenotype, and reduced expression of exhaustion markers. scRNA-seq further demonstrated that CD8αβ⁺ γδT cells upregulated genes involved in DNA replication and repair. Our findings indicate that CD8αβ⁺ γδT cells upregulate molecules associated with activation and function during P. yoelii infection, suggesting that they may play a more prominent role in host defence against malaria.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 7","pages":"e70091"},"PeriodicalIF":1.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148369530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycocalyx-Driven Immunomodulation in Trypanosoma cruzi: Structures, Host Responses, Diagnostic and Therapeutic Targeting.","authors":"Norton Heise, Christopher Mark West, Carolina Macedo Koeller","doi":"10.1111/pim.70092","DOIUrl":"10.1111/pim.70092","url":null,"abstract":"<p><p>Chagas disease, caused by Trypanosoma cruzi, remains an important neglected infection due to underdiagnosis, global spread resulting from increased migration of people infected with T. cruzi and concomitant organ transplantation and blood transfusion, and limited availability of chemotherapy. The parasite's surface is covered by a dense glycocalyx enriched in GPI-anchored mucins, trans-sialidases, and glycoinositolphospholipids (GIPLs), which collectively shape host-parasite interactions. Here we synthesize structural and biosynthetic features of key glycoconjugates and discuss how they modulate innate and adaptive immunity through pattern-recognition receptors (e.g., TLR2/6 and TLR4), inhibitory lectins (e.g., Siglec-E), extracellular vesicle signalling, and complement evasion mediated by TS-like regulators (T-DAF, TcCRP) and factor H recruitment. We highlight how strain- and stage-specific glycan variation, including α-Galp- and β-Galf-containing epitopes, influences immune recognition, pathogenesis, and persistence. Finally, we evaluate translational opportunities: parasite-selective targeting of sugar-nucleotide metabolism and glycosyltransferases, and development of defined glycoepitopes (glycotopes) as improved biomarkers for diagnosis and post-treatment monitoring. Together, these insights position the T. cruzi glycocalyx as a central driver of immunomodulation and a promising source of therapeutic, vaccine and diagnostic targets.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 7","pages":"e70092"},"PeriodicalIF":1.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13353147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148423178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Immunoinformatic Approach for a Multi-Epitope Vaccine Against Toxoplasma gondii.","authors":"Negar Asadi, Leila Navapour, Navid Mogharrab, Elham Yousefi, Sadegh Feizollahzadeh, Mortaza Taheri-Anganeh, Shahram Khademvatan, Gordon S Howarth","doi":"10.1111/pim.70095","DOIUrl":"10.1111/pim.70095","url":null,"abstract":"<p><p>Infection with the intracellular apicomplexan parasite Toxoplasma gondii causes severe and often fatal clinical outcomes worldwide, especially in patients with immunodeficiency, diabetes and in pregnant women and infants. Despite approximately one-third of the global population being infected with T. gondii, there is currently no effective vaccine available for humans. The objective was to develop a potential vaccine candidate for T. gondii, which would incorporate the B- and T-lymphocyte epitopes derived from three immunogenic antigens of the parasite. Initially, the immunodominant epitopes present in the SAG1, GRA6 and GRA7 proteins of T. gondii were identified. Following this, a multi-epitope vaccine was developed by integrating B-cell epitopes, CTL epitopes and HTL epitopes, with the addition of the 50S ribosomal protein L7/L12 serving as an adjuvant to enhance the immunogenic properties of the vaccine. All identified epitopes demonstrated characteristics of being antigenic, nonallergenic, nontoxic and lacking human homologues. Furthermore, the candidate vaccine exhibited immunogenicity, non-allergenicity and stability. Molecular docking studies indicated robust interactions between the vaccine construct and the TLR-4 immune receptor. Additionally, the stability of the formulated vaccine was confirmed through molecular dynamic simulations. In silico analyses suggested that the vaccine construct could effectively initiate primary immune responses; however, further laboratory evaluations are required to verify its efficacy and safety.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 7","pages":"e70095"},"PeriodicalIF":1.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No Simple Fluke: Schistosomiasis as an Emerging Regulator of Haematopoiesis.","authors":"Shinjini Chakraborty","doi":"10.1111/pim.70094","DOIUrl":"10.1111/pim.70094","url":null,"abstract":"<p><p>Schistosomiasis, or bilharzia, is a highly prevalent water-borne helminth infection that accounts for an estimated 1.5-1.7 billion disability-adjusted life years lost annually. Pathology driven by adult worms and eggs is accompanied by robust immunomodulation in the human host. Protective responses may promote worm elimination, limit bystander tissue injury caused by parasite migration and contain eggs within granulomatous lesions. However, evidence also suggests that schistosomes can actively or indirectly influence haematopoiesis, thereby reshaping downstream mature immune cell responses. This perspective reviews current literature on schistosome-dependent and host-derived regulation of haematopoiesis, the importance of preclinical modelling and the emerging relevance of controlled human challenge models. It also discusses bone marrow organoid models and their utility for recapitulating complex infection dynamics, with the aim of informing clinically relevant studies and therapeutic strategies.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 7","pages":"e70094"},"PeriodicalIF":1.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13376223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No Evidence for Association Between ICOS (a T-Cell Co-Stimulatory Molecule) Gene Polymorphisms and Anti-MSP-1₁₉ IgG Response in Venezuelan Endemic Plasmodium vivax Malaria.","authors":"Rublee D Sevilla, Oriana A Regalado-Gutiérrez, Albina Wide, Rafael Puche-Quiñonez, Manuel A Patarroyo, Oscar Noya-González, Mercedes Fernández-Mestre","doi":"10.1111/pim.70086","DOIUrl":"10.1111/pim.70086","url":null,"abstract":"<p><p>The blood-stage merozoite surface protein 1 (PvMSP₁₉) of Plasmodium vivax is a key target of naturally acquired antibodies. Effective humoral responses depend on T-cell co-stimulation, notably via the inducible co-stimulator (ICOS) molecule. Polymorphisms in the ICOS gene may influence antibody production, yet this relationship remains unexplored in naturally infected populations. We analysed 91 individuals with uncomplicated P. vivax infection in Venezuela. Total IgG antibodies against recombinant PvMSP₁₉ were measured by ELISA. A two-step cluster analysis based on antibody reactivity indices (RI) was employed to categorize participants as low, medium, or high responders. Genotyping of ICOS polymorphisms (rs4404254, rs4675379 and rs10183087) was performed using PCR-based methods. Haplotype frequencies (inferred via the Expectation-Maximization algorithm), linkage disequilibrium (LD) and associations under various genetic inheritance models were assessed using Haplo.stats (R environment) and SNPStats. PvMSP₁₉-specific IgG was detected in 70.3% of participants. The optimal three-cluster solution (silhouette coefficient = 0.7) revealed significant differences in median RI across low (0.408), medium (0.862) and high responders (1.267; p < 0.001). ICOS genotypes and haplotypes showed no significant associations with antibody levels across any inheritance models, although strong LD was observed among the three loci (p < 0.05). Notably, antibody responses positively correlated with the number of prior malarial episodes (r = 0.803, p < 0.0001). Our results indicate that the studied ICOS polymorphisms do not significantly affect IgG responses against PvMSP₁₉ in this population, suggesting that variability in other costimulatory molecules may more strongly influence humoral immunity to P. vivax. These findings highlight the complexity of T-cell-mediated regulation of antibody responses and provide insights for optimizing vaccine strategies targeting blood-stage malaria antigens.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 6","pages":"e70086"},"PeriodicalIF":1.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148043276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}