Parasite Immunology最新文献

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Simultaneous Infection With Genetically Distinct Trypanosoma cruzi Isolates Is Associated With Distinct Myocardial Innate Immune Transcriptional Profiles During Acute Infection in Mice. 在小鼠急性感染期间,同时感染遗传上不同的克氏锥虫分离株与不同的心肌先天免疫转录谱相关。
IF 1.2 4区 医学
Parasite Immunology Pub Date : 2026-10-01 DOI: 10.1111/pim.70103
George Harisson Felinto Sampaio, Andressa Noronha Barbosa-Silva, Carlos Ramon do Nascimento Brito, Lucas Abrantes Batista, Christiane Carlos Araújo de Negreiros, Ramayana Morais de Medeiros Brito, Rand Randall Martins, Manuela Sales Lima Nascimento, Antonia Claudia Jácome da Câmara, Paulo Marcos da Matta Guedes, Lúcia Maria da Cunha Galvão
{"title":"Simultaneous Infection With Genetically Distinct Trypanosoma cruzi Isolates Is Associated With Distinct Myocardial Innate Immune Transcriptional Profiles During Acute Infection in Mice.","authors":"George Harisson Felinto Sampaio, Andressa Noronha Barbosa-Silva, Carlos Ramon do Nascimento Brito, Lucas Abrantes Batista, Christiane Carlos Araújo de Negreiros, Ramayana Morais de Medeiros Brito, Rand Randall Martins, Manuela Sales Lima Nascimento, Antonia Claudia Jácome da Câmara, Paulo Marcos da Matta Guedes, Lúcia Maria da Cunha Galvão","doi":"10.1111/pim.70103","DOIUrl":"10.1111/pim.70103","url":null,"abstract":"<p><p>Innate immune receptors are central to host resistance against Trypanosoma cruzi infection, yet how parasite genetic diversity is associated with these responses remains poorly understood. Here, we characterized acute infection outcomes and myocardial innate immune transcriptional profiles in mice subjected to single and mixed infections with genetically distinct T. cruzi parasites (DTUs TcII, TcIII, and TcVI). Swiss mice were infected with RN2, RN23, Y, or CL-Brener individually or in combination, and parasitemia, survival, and cardiac gene expression were assessed. The Y strain, CL-Brener clone, and RN2 + RN23 + CL-Brener condition exhibited a high-severity profile, with marked parasitemia (8000-28,000 trypomastigotes/5 μL), mortality of 74%-100%, reduced myocardial transcription of Tlr2, Tlr4, Tlr9, Trif, and Myd88, and increased transcription of Nlrp3, Casp1, Il1β, and Tnfα. In contrast, RN2 and RN23 single infections exhibited low-severity profiles and higher transcription of innate immune mediators associated with parasite control. Mixed-infection groups displayed transcriptional and infection profiles differing from the corresponding single-infection groups under a standardized total inoculum. Together, these findings identify distinct myocardial innate immune transcriptional profiles across single and mixed T. cruzi infection conditions and support further investigation of the contributions of parasite population composition and dose to acute infection outcomes.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 10","pages":"e70103"},"PeriodicalIF":1.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113422","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}
引用次数: 0
Decoding the Clinical Spectrum of Amoebiasis Immune Mechanisms: Cytokine Balance and Multi-Matrix SIgA (Saliva, Urine and Serum) as Prognostic Biomarkers. 解码阿米巴病免疫机制的临床谱:细胞因子平衡和多基质SIgA(唾液、尿液和血清)作为预后生物标志物。
IF 1.2 4区 医学
Parasite Immunology Pub Date : 2026-10-01 DOI: 10.1111/pim.70106
Payam I Jibrael, Hiro M Obaid
{"title":"Decoding the Clinical Spectrum of Amoebiasis Immune Mechanisms: Cytokine Balance and Multi-Matrix SIgA (Saliva, Urine and Serum) as Prognostic Biomarkers.","authors":"Payam I Jibrael, Hiro M Obaid","doi":"10.1111/pim.70106","DOIUrl":"https://doi.org/10.1111/pim.70106","url":null,"abstract":"<p><p>Entamoeba histolytica infection exhibits a range of clinical consequences, spanning from asymptomatic carriage to severe symptomatic disease. Despite comprehensive research on symptomatic E. histolytica infection, limited attention has been given to asymptomatic cases, notably in interpreting the immune activation and regulatory pathways that allow parasite sustainability without observable disease. This study aimed to evaluate the participation of pro-inflammatory cytokines [tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ)], anti-inflammatory cytokines (interleukin-10 [IL-10], interleukin-4 [IL-4]) and mucosal antibodies (secretory IgA [SIgA]) in distinguishing sexes, symptomatic and asymptomatic infections and elucidating their role in amoebiasis. Only serum SIgA exhibited significant sex-based differences among all immune parameters, suggesting the impact of sex hormones on the systemic immune regulation rather than the localized immunity. Serum cytokine levels were assessed and statistically evaluated across symptomatic, asymptomatic and control groups. TNF-α and IFN-γ levels were significantly increased in the symptomatic group (p < 0.01), reflecting a robust inflammation associated with tissue destruction and clinical symptoms. Conversely, IL-10 was significantly greater in the asymptomatic group, indicating a protective role in dampening intense inflammation and sustaining parasite persistence without obvious clinical symptoms. IL-4 levels did not differ significantly among groups, suggesting limited involvement of this cytokine in the immunopathology of amoebiasis. Similarly, SIgA concentrations in saliva, urine and serum specimens were consistently heightened in the symptomatic group, indicating mucosal immune promotion. Receiver operating characteristic (ROC) curve analysis demonstrated that cytokine ratios (TNF-α/IL-10, IFN-γ/IL-10) with serum, urinary and salivary SIgA levels showed high discrimination between symptomatic and asymptomatic groups, thereby demonstrating strong prognostic accuracy. These findings emphasize the crucial role of cytokine balance and mucosal antibody reactions in determining the clinical trajectory of E. histolytica infection, highlighting the clinical utility of quantifying these biomarkers for the diagnosis and differentiation of amoebiasis.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 10","pages":"e70106"},"PeriodicalIF":1.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113418","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}
引用次数: 0
Vaccination With Trichuris muris Poly-Cysteine and Histidine-Tailed Protein p43 Protects Against Chronic Infection. 接种鼠毛线虫多半胱氨酸和组氨酸尾蛋白p43预防慢性感染
IF 1.2 4区 医学
Parasite Immunology Pub Date : 2026-10-01 DOI: 10.1111/pim.70107
Allison J Bancroft, Kelly S Hayes, Laura Campbell, Seona Thompson, Christina Dold, Luke Blackwell, Christine S Rollier, David J Thornton, Richard K Grencis
{"title":"Vaccination With Trichuris muris Poly-Cysteine and Histidine-Tailed Protein p43 Protects Against Chronic Infection.","authors":"Allison J Bancroft, Kelly S Hayes, Laura Campbell, Seona Thompson, Christina Dold, Luke Blackwell, Christine S Rollier, David J Thornton, Richard K Grencis","doi":"10.1111/pim.70107","DOIUrl":"https://doi.org/10.1111/pim.70107","url":null,"abstract":"<p><p>Trichuris trichiura is one of the soil transmitted geohelminths which together currently affect approximately 25% of the global population resulting in considerable morbidity particularly in children and young adults. Recent estimates put infection by T. trichiura at approximately 513 million. De-worming programmes are often not completely effective against T. trichiura and fail to provide resistance to reinfection. Vaccination against these multicellular parasites has proved difficult as they have complex antigenic make-up and the potential to harness the host immune system to their own advantage. Previous vaccination experiments in mice using excretory secretory (ES) material have proved successful although the specific antigens responsible for protection have remained elusive. Here we show that vaccination of mice with native (n)p43, the dominant secreted protein from adult T. muris, formulated with Alum adjuvant can protect against chronic infection. The vaccine candidate generated a strong Type 2 response and host protection was dependent on signalling through IL-4 Rα. Vaccination with a recombinant (r)p43 formulated with alum resulted in stunted worms and reduced worm fecundity but no significant reduction in worm burden. Deglycosylation of np43 significantly abrogated protection against infection suggesting p43 glycans play a role in mediating the protective efficacy of np43. Vaccination using an adenoviral p43 construct generated a robust antibody response to np43 but no protection against challenge infection. Orthologues of p43 are present in other closely related nematodes including T. trichiura and T. suis which infects wild and domestic pigs, suggesting potential for similar vaccine development for both human and veterinary trichiuriasis.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 10","pages":"e70107"},"PeriodicalIF":1.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113469","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}
引用次数: 0
Impact of Prior Exposure to Anisakis simplex Antigens on Immune Response During SARS-CoV-2 Vaccination. 单纯异尖akis抗原对SARS-CoV-2疫苗接种期间免疫应答的影响
IF 1.2 4区 医学
Parasite Immunology Pub Date : 2026-09-01 DOI: 10.1111/pim.70101
Carmen Cuéllar, Marta Rodero, Juan González-Fernández, Lorena Galindo-Regal, Francisca López-Chuliá, Carlos García-Ballesteros, Leonor Fernández-Murga, Antonio Llombart-Cussac, María Victoria Domínguez-Márquez, Juan Carlos Andreu-Ballester
{"title":"Impact of Prior Exposure to Anisakis simplex Antigens on Immune Response During SARS-CoV-2 Vaccination.","authors":"Carmen Cuéllar, Marta Rodero, Juan González-Fernández, Lorena Galindo-Regal, Francisca López-Chuliá, Carlos García-Ballesteros, Leonor Fernández-Murga, Antonio Llombart-Cussac, María Victoria Domínguez-Márquez, Juan Carlos Andreu-Ballester","doi":"10.1111/pim.70101","DOIUrl":"10.1111/pim.70101","url":null,"abstract":"<p><p>Parasitic infections can induce immunomodulatory effects that may influence host responses to vaccination. Chronic exposure to Anisakis antigens could modify T-cell and antibody profiles, potentially affecting SARS-CoV-2 vaccine effectiveness in endemic populations. We aimed to determine whether prior exposure to Anisakis alters SARS-CoV-2 vaccine-induced immunity. Forty healthy volunteers were evaluated at five time points before and after receiving either the Pfizer-BioNTech or Oxford-AstraZeneca COVID-19 vaccines. Serum levels of anti-Anisakis and anti-SARS-CoV-2 antibodies were quantified by ELISA, whereas T- and B-cell subsets and apoptosis rates were analysed by flow cytometry. SARS-CoV-2 vaccination induced significant changes in anti-Anisakis antibody levels, particularly IgG and IgA, which increased after the second dose and persisted throughout follow-up. Individuals seropositive for anti-Anisakis antibodies exhibited higher post-vaccination anti-SARS-CoV-2 IgG levels, and anti-Anisakis IgA positivity correlated with stronger anti-SARS-CoV-2 IgA responses at specific time points. Positive associations were also observed between anti-Anisakis antibody levels and circulating T- and B-cell subsets. Prior sensitization to Anisakis antigens appears to influence both the magnitude and quality of the adaptive immune response elicited by SARS-CoV-2 vaccination, affecting antibody profiles and lymphocyte subset dynamics. Conversely, COVID-19 vaccination can alter humoral reactivity to Anisakis antigens, indicating bidirectional immunomodulation between parasite exposure and vaccine-induced immunity.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 9","pages":"e70101"},"PeriodicalIF":1.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977681","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}
引用次数: 0
Egg Deposition-Associated Immune Transition and Tfh-Like Humoral Features During Schistosoma japonicum Infection in Mice. 日本血吸虫感染小鼠卵沉积相关免疫转变和tfh样体液特征
IF 1.2 4区 医学
Parasite Immunology Pub Date : 2026-09-01 DOI: 10.1111/pim.70100
Zhen Tang, Tingyu Zhou, Wanping Luo, Mingyi Shui, Jiaxuan Zhang, Cuiping Liu, Xiaoting Wang
{"title":"Egg Deposition-Associated Immune Transition and Tfh-Like Humoral Features During Schistosoma japonicum Infection in Mice.","authors":"Zhen Tang, Tingyu Zhou, Wanping Luo, Mingyi Shui, Jiaxuan Zhang, Cuiping Liu, Xiaoting Wang","doi":"10.1111/pim.70100","DOIUrl":"https://doi.org/10.1111/pim.70100","url":null,"abstract":"<p><p>Schistosoma japonicum infection causes egg-induced hepatic granulomatous inflammation together with extensive remodelling of host immunity. Although infection is known to progress from early Th1-associated immunity to egg-driven type 2 responses, the temporal relationships among egg-induced pathology, CD4+ T-cell polarization, T follicular helper (Tfh)-like phenotypes and parasite-specific humoral immunity remain incompletely defined. We therefore infected BALB/c mice with S. japonicum and examined them at serial time points after infection, assessing hepatic histopathology, serum ALT and AST activities, T-cell frequencies, cytokine-producing CD4+ T cells, helper-lineage transcription factors, PD-1 and ICOS expression on T cells, PD-L1 and ICOSL expression on B cells, CXCR5+ICOS+ phenotypic Tfh-like cells and serum SEA-specific IgG, with five biologically independent mice at each time point. Egg-associated hepatic granulomas first became apparent at week 5, enlarged during the middle stage of infection and regressed at later time points. Early infection was characterized by increased IFN-γ-producing CD4+ T cells and elevated Tbx21 expression; following egg deposition, IL-4-, IL-17A- and IL-21-producing CD4+ T cells and Gata3, Rorc and Bcl6 expression increased, and PD-1 and ICOS on CD4+ T cells together with PD-L1 and ICOSL on B cells changed dynamically over the course of infection. By week 8, CXCR5+ICOS+ Tfh-like cells were increased in the spleen, mesenteric lymph nodes and peripheral blood, and SEA-specific IgG had risen markedly after egg deposition and correlated positively with the frequency of splenic CXCR5+ICOS+ CD4+ T cells (r<sub>s</sub> = 0.3979, p < 0.001). Egg deposition thus represents a temporal immunological transition point in S. japonicum infection: the onset of egg-induced hepatic pathology coincides with the shift from early Th1-associated features to Th2-, Th17-, Tfh-like and SEA-specific humoral responses.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"48 9","pages":"e70100"},"PeriodicalIF":1.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001733","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}
引用次数: 0
Hepatic Granulomatous Inflammation and Angiogenesis Upregulation Provoked by Acanthamoeba polyphaga Infection and Role of Quercetin-Conjugated Silver Nanoparticles. 多食棘阿米巴感染引起的肝脏肉芽肿炎症和血管生成上调及槲皮素共轭银纳米颗粒的作用。
IF 1.2 4区 医学
Parasite Immunology Pub Date : 2026-09-01 DOI: 10.1111/pim.70098
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
{"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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542306/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Disruption of the CD47-SIRPα Axis Causes Profound Reduction of Parasitaemia in Mice Infected With Babesia microti. CD47-SIRPα轴的破坏导致感染巴贝虫的小鼠寄生虫血症的显著减少
IF 1.2 4区 医学
Parasite Immunology Pub Date : 2026-08-01 DOI: 10.1111/pim.70099
Shamim Mohammad, Ioana Brasov, Susan Gottshall, Sarah Robins, Sujatha Rashid, Rebecca Bradford, Robert E Molestina
{"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<sup>-/-</sup>) 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<sup>-/-</sup> 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<sup>-/-</sup> 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}
引用次数: 0
Attenuation of Tau Hyperphosphorylation by Chronic Toxoplasma gondii Infection in a Mouse Model of Alzheimer's Disease. 慢性弓形虫感染阿尔茨海默病小鼠模型中Tau过度磷酸化的衰减
IF 1.2 4区 医学
Parasite Immunology Pub Date : 2026-08-01 DOI: 10.1111/pim.70096
Seung-Hwan Seo, Ji-Eun Lee, Eun-Ji Cho, Eun-Hee Shin
{"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}
引用次数: 0
Cytotoxic CD4+ T Cells in Visceral Leishmaniasis Patients. 内脏利什曼病患者的细胞毒性CD4+ T细胞。
IF 1.2 4区 医学
Parasite Immunology Pub Date : 2026-08-01 DOI: 10.1111/pim.70097
Shashi Bhushan Chauhan, Siddharth Sankar Singh, Bhawana Singh, Shashi Kumar, Rahul Tiwari, Vibhav Gautam, Fabian Rivera, Susanne Nylen, Christian Engwerda, Shyam Sundar, Rajiv Kumar
{"title":"Cytotoxic CD4<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> T-cell responses are ineffective for reasons that are still unclear. Our recent study reporting a transcriptional signature of CD4<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> 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}
引用次数: 0
Characteristics of Splenic CD8αβ+ γδT Cells in Plasmodium yoelii Infection. 脾CD8αβ+ γδT细胞在约氏疟原虫感染中的特征
IF 1.2 4区 医学
Parasite Immunology Pub Date : 2026-07-01 DOI: 10.1111/pim.70091
Xingfei Pan, Li Pan, Xingyue Wang, Meiling Liu, Haiwen Yuan, Mingjie Chen, Xiongyu Xie, Qi Ye, Lixin Luo, Guikuan Liang, Hongyan Xie, Jun Huang
{"title":"Characteristics of Splenic CD8αβ<sup>+</sup> 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<sup>+</sup> γδT cells, a distinct subset of γδT cells, remains poorly characterized during malaria infection. Female C57BL/6 mice were intraperitoneally injected with 1 × 10<sup>6</sup> 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<sup>+</sup> γδT cells. Meanwhile, CD45<sup>+</sup> lymphocytes were sorted for single-cell RNA sequencing (scRNA-seq) to compare differentially expressed genes between CD8αβ<sup>+</sup> γδT and CD8αα<sup>+</sup> γδT cell subsets. FACS analysis revealed a significant increase in CD8αβ<sup>+</sup> 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<sup>+</sup> γδT cells upregulated genes involved in DNA replication and repair. Our findings indicate that CD8αβ<sup>+</sup> 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}
引用次数: 0
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