Wesam M A Elgendy, Ahmad A Othman, Basma N Khalifa, Nema A Soliman, Dareen Mohamed, Salwa S Younis
{"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}
Norton Heise, Christopher Mark West, Carolina Macedo Koeller
{"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}
Negar Asadi, Leila Navapour, Navid Mogharrab, Elham Yousefi, Sadegh Feizollahzadeh, Mortaza Taheri-Anganeh, Shahram Khademvatan, Gordon S Howarth
{"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}
Rublee D Sevilla, Oriana A Regalado-Gutiérrez, Albina Wide, Rafael Puche-Quiñonez, Manuel A Patarroyo, Oscar Noya-González, Mercedes Fernández-Mestre
{"title":"No Evidence for Association Between ICOS (a T-Cell Co-Stimulatory Molecule) Gene Polymorphisms and Anti-MSP-1<sub>19</sub> 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 (PvMSP<sub>19</sub>) 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 PvMSP<sub>19</sub> 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. PvMSP<sub>19</sub>-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 PvMSP<sub>19</sub> 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}
Francieli Marinho Carneiro, Débora Oliveira Dos Santos, Roberto Mitsuyoshi Hiramoto, Noemi Nosomi Taniwaki, Gislene Mitsue Namiyama, Jose Eduardo Tolezano, Vera Lucia Pereira-Chioccola
{"title":"Leishmania (Leishmania) Infantum Living in Nature Secretes a Higher Concentration of Extracellular Vesicles, Suggesting Greater Infectious Potential.","authors":"Francieli Marinho Carneiro, Débora Oliveira Dos Santos, Roberto Mitsuyoshi Hiramoto, Noemi Nosomi Taniwaki, Gislene Mitsue Namiyama, Jose Eduardo Tolezano, Vera Lucia Pereira-Chioccola","doi":"10.1111/pim.70089","DOIUrl":"10.1111/pim.70089","url":null,"abstract":"<p><p>Visceral leishmaniasis (VL) is a chronic systemic disease that, without proper treatment, can be fatal. Extracellular vesicles released by Leishmania species (Leish-EVs) perform various functions, including modulation of the host's immune system and inflammatory responses. This study investigated whether Leish-EVs produced by circulating strains of Leishmania (Leishmania) infantum exhibited the same pattern of cytokine stimulation and modulation of inflammatory and pro-inflammatory responses as those produced by a standard strain maintained for many years in different laboratories. The assays were performed using Leish-EVs released by promastigotes of the two L. (L.) infantum strains. The Standard strain was L. (L.) infantum (MHOM/BR/1972/LD), maintained under laboratory conditions, while the Natural strain was L. (L.) infantum recently isolated from a dog living in an endemic region of São Paulo State, Brazil. Both strains were cultivated in 199 medium and, during the logarithmic growth phase, promastigotes were prepared for excretion of Leish-EVs according to previously established protocols. The Natural strain, when compared with the Standard strain, produced a higher concentration of Leish-EVs, which stimulated THP-1 cells to release large amounts of THP-1-EVs (EVs produced by THP-1 cells). In addition, stimulation of THP-1 cells with Leish-EVs induced high expression of miR-21-5p and miR-146a-5p, as well as cytokines IL-10, IL-12, and particularly TGF-β. These findings suggest that Leish-EVs released by strains living in nature have greater immunomodulatory potential than those produced by strains maintained in laboratories, impacting both miRNA regulation and cytokine expression.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 6","pages":"e70089"},"PeriodicalIF":1.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218710","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}
Amir Hessam Shakeri, Saeid Vahedi, Samira Saedi, Sousan Houshmandi, Seyed Mohamad Javad Shokouhian, Nader Khani, Aziz Homayouni-Rad, Ramin Khorrami
{"title":"Potential of Postbiotics as Antiparasitic Agents.","authors":"Amir Hessam Shakeri, Saeid Vahedi, Samira Saedi, Sousan Houshmandi, Seyed Mohamad Javad Shokouhian, Nader Khani, Aziz Homayouni-Rad, Ramin Khorrami","doi":"10.1111/pim.70087","DOIUrl":"10.1111/pim.70087","url":null,"abstract":"<p><p>Gastrointestinal parasitic infections are considered a significant public health concern with widespread global prevalence. The pathological processes arising from these infections contribute to numerous public health challenges, particularly in tropical and subtropical regions. Prevention and management primarily rely on the administration of anthelmintic and antiprotozoal drugs; however, the growing prevalence of drug resistance poses a major obstacle to the complete eradication of parasitic infections in both humans and livestock. This highlights the need for exploring alternative strategies. The use of beneficial microorganisms, particularly probiotics and their metabolites (known as postbiotics), has gained significant interest due to their potential prophylactic benefits against various diseases, including parasitic infections. Recent research on the interactions between postbiotics, parasites, and host immune cells through both animal models and in vitro culture systems has seen substantial growth. Postbiotics exert antiparasitic effects through multiple mechanisms, including disruption of parasite membrane integrity, inhibition of key metabolic enzymes, induction of oxidative stress, interference with attachment and invasion, modulation of host immune responses, and alteration of the intestinal microenvironment to hinder parasite survival. This review will focus on the effects of postbiotics and their mechanisms of action against helminths and protozoan parasites, both of which are relevant to gastrointestinal health.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 6","pages":"e70087"},"PeriodicalIF":1.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148056003","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}
Chih-Cheng Chuang, Wen-Bin Wu, Jiun-Jr Wang, Ming-Chieh Ma, Wen-Yuan Du
{"title":"IL-25 Enhances Eosinophil-Associated Inflammation in Angiostrongylus cantonensis-Infected Mice.","authors":"Chih-Cheng Chuang, Wen-Bin Wu, Jiun-Jr Wang, Ming-Chieh Ma, Wen-Yuan Du","doi":"10.1111/pim.70088","DOIUrl":"10.1111/pim.70088","url":null,"abstract":"<p><p>This study aimed to investigate the role of interleukin (IL)-25 in the pathogenesis of angiostrongylosis. We used ICR mice as non-permissive hosts, divided them into groups and experimentally infected them with infective larvae of the Angiostrongylus cantonensis. Two groups of infected mice were injected intraperitoneally with either mouse IL-25 or an anti-IL-25 monoclonal antibody (mAb) at 3 days post-infection (dpi), followed by booster injections at the same dose every 5 days. Serum samples and brain tissues were collected weekly from each group for immunological and pathological examinations. The IL-25-treated group exhibited significant increases in eosinophil percentages and levels of immunoglobulin E (IgE), as well as in the levels of IL-5 and IL-13. The severity of eosinophilic meningitis was exacerbated in the IL-25-treated group 21 dpi. These results suggest that IL-25 may enhance eosinophil-associated inflammation in mice infected with A. cantonensis.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 6","pages":"e70088"},"PeriodicalIF":1.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13242975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199665","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}
Hangyu Li, Yuanli Gao, Yongling Fan, Biao He, Nie Tan, Shuai Guo, Wenyue Xu, Taiping Liu
{"title":"T-Bet Modulates Plasmodium-Specific CD4<sup>+</sup> T Cell Differentiation and Anti-Malarial Immunity During Blood-Stage Infection.","authors":"Hangyu Li, Yuanli Gao, Yongling Fan, Biao He, Nie Tan, Shuai Guo, Wenyue Xu, Taiping Liu","doi":"10.1111/pim.70090","DOIUrl":"https://doi.org/10.1111/pim.70090","url":null,"abstract":"<p><p>CD4<sup>+</sup> T helper (Th)1 cells are theorized to control Plasmodium parasite burden during blood-stage malaria. However, their exact role in controlling parasitemia in vivo remains inadequately characterized. Here, we used a CD4<sup>+</sup> T cell-restricted Cre-Lox T-bet (the master regulator of Th1 cells) excision mouse model to examine the role of Plasmodium-specific Th1 cell responses in controlling blood-stage infection. Our results found that T-bet deficiency in CD4<sup>+</sup> T cells markedly enhanced the growth of blood-stage Plasmodium yoelii (P. yoelii) 17XNL and Plasmodium chabaudi (P. chabaudi) AS, but not Plasmodium berghei (P. berghei) ANKA. Although T-bet deficiency in CD4<sup>+</sup> T cells did not significantly impair the generation of pathogen-specific GC-Tfh cells, GC B cells, or the production of Plasmodium-specific antibodies, it profoundly suppressed Plasmodium-specific Th1 differentiation and IFN-γ production. Conversely, T-bet deficiency selectively promoted Plasmodium-specific Th17 differentiation without affecting other Th subsets. However, despite the heightened Th17 cell responses, in vivo neutralization of IL-17A did not impact host defence against P. yoelii 17XNL infection. Collectively, our data demonstrate that T-bet in CD4<sup>+</sup> T cells enhances Plasmodium-specific Th1 cell responses while restraining Plasmodium-specific Th17 cell differentiation. In addition, Plasmodium-specific Th1 cells can confer substantial protection against blood-stage malaria. These findings support the development of effective malaria vaccines designed to elicit robust CD4<sup>+</sup> Th1 responses.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 6","pages":"e70090"},"PeriodicalIF":1.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148302878","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}
Paulo Henrique Tolentino Moura, Beatriz Prado Noronha, Marcio Sobreira Silva Araujo, Marcela Lima Moreira, Diego Patrick Soares Lopes, Rodrigo Gentil Miquilino de Oliveira, Waldemar de Paula Junior, Marileia Chaves Andrade
{"title":"Alcohol Pre-Exposure in T. cruzi-Infected Mice Enhances IL-4 Production by CD8 T Cells and Modulates Innate Immunity Cytokine Response.","authors":"Paulo Henrique Tolentino Moura, Beatriz Prado Noronha, Marcio Sobreira Silva Araujo, Marcela Lima Moreira, Diego Patrick Soares Lopes, Rodrigo Gentil Miquilino de Oliveira, Waldemar de Paula Junior, Marileia Chaves Andrade","doi":"10.1111/pim.70081","DOIUrl":"10.1111/pim.70081","url":null,"abstract":"<p><p>Trypanosoma cruzi infection, which causes Chagas' disease, induces an immune response in the host whose efficiency is important for the infection to persist or be eliminated. Alcohol consumption produces a great impact on the immune system, inducing alterations in the determination of T lymphocyte effector function, directing the profile of these cells to tolerance or inflammation. Our study aimed to evaluate, in C57BL/6 mice, the cytokine production in splenic leukocytes from T. cruzi infected and treated (EtOH) for 15 days and controls. Twenty-four mice were randomised into four groups, with 12 animals each: (1) Non-Infected Control (NI), (2) Control Infected (CI), (3) Experimental Non-Infected (EtOH<sub>-</sub>NI), and (4) Experimental Infected (EtOH-I). Ethanol-pre-exposed infected mice exhibited elevated parasitaemia during the patent period compared to controls. Adaptive immunity was characterised by increased IL-4, IL-10 and IFN-γ production by CD8+ T lymphocytes, while innate immunity showed reduced cytokine production, particularly in NK cells and macrophages. Ethanol amplified IL-10 and IFN-γ responses in macrophages yet suppressed TNF-α production in dendritic cells and macrophages during infection. These findings suggest ethanol modulates the immune response by enhancing adaptive immunity while impairing innate mechanisms, contributing to altered host-pathogen dynamics in T. cruzi infection.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 5","pages":"e70081"},"PeriodicalIF":2.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147964355","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}