Immune training enhances anti-viral responses and improves outcomes in Pax5 −/+ mice susceptible to chronic infection
Abstract Viral infections pose a significant global burden. Host susceptibility to pathogens is determined by many factors including genetic variation that can lead to immunodeficient or dysregulated antiviral immune responses. Pax5 heterozygosity (Pax5 −/+), resulting in reduced PAX5 levels in mice...
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Springer Nature
2025-03-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.1038/s44321-025-00208-4 |
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| author | Zhe Lu Olivia Stencel Wei Liu Eleni Vasileiou Haifeng C Xu Piyush Pandey Paweł Stachura Abdelrahman Elwy Anastassia Tsombal Ann-Sophie Mai Franziska Auer Mina N F Morcos Maximilian Seidl Sarah Koziel Peter-Martin Bruch Sascha Dietrich Sarah Elitzur Gunther Hartmann Karl S Lang Stefan Janssen Ute Fischer Sanil Bhatia Philipp A Lang Arndt Borkhardt Julia Hauer Aleksandra A Pandyra |
| author_facet | Zhe Lu Olivia Stencel Wei Liu Eleni Vasileiou Haifeng C Xu Piyush Pandey Paweł Stachura Abdelrahman Elwy Anastassia Tsombal Ann-Sophie Mai Franziska Auer Mina N F Morcos Maximilian Seidl Sarah Koziel Peter-Martin Bruch Sascha Dietrich Sarah Elitzur Gunther Hartmann Karl S Lang Stefan Janssen Ute Fischer Sanil Bhatia Philipp A Lang Arndt Borkhardt Julia Hauer Aleksandra A Pandyra |
| author_sort | Zhe Lu |
| collection | DOAJ |
| description | Abstract Viral infections pose a significant global burden. Host susceptibility to pathogens is determined by many factors including genetic variation that can lead to immunodeficient or dysregulated antiviral immune responses. Pax5 heterozygosity (Pax5 −/+), resulting in reduced PAX5 levels in mice, mimics germline or somatic PAX5 dysregulation contributing to diseases such as childhood B-cell precursor acute lymphoblastic leukemia (B-ALL). In contrast to the well-characterized roles of PAX5 during early B-cell development, little is known about how Pax5 heterozygosity impacts antiviral responses. We infected Pax5 −/+ mice with the noncytopathic Lymphocytic Choriomeningitis Virus (LCMV) and found that infection with the chronic Docile strain resulted in decreased survival of Pax5 −/+ mice. While early adaptive CD8+ T-cell (CTL) immunity was robust in Pax5 −/+ mice, LCMV-specific neutralizing antibody production was compromised leading to impaired long-term viral clearance and a pro-inflammatory milieu in the bone marrow (BM). Here we show that survival outcomes were improved upon prophylactic treatment with the β-glucan immune trainer through induction of heterologous protection against chronic infection. β-Glucan enhanced viral clearance, CTL immunity, neutralizing antibody production and reduced monocyte immunosuppression in multiple LCMV-resident host organs. New insight from this study will help design effective prophylactic treatment strategies against chronic viral infections, particularly in genetically predisposed susceptible hosts. |
| format | Article |
| id | doaj-art-2d44ad874bbf4c8b833e156fddacebeb |
| institution | DOAJ |
| issn | 1757-4684 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-2d44ad874bbf4c8b833e156fddacebeb2025-08-20T03:10:18ZengSpringer NatureEMBO Molecular Medicine1757-46842025-03-0117469672110.1038/s44321-025-00208-4Immune training enhances anti-viral responses and improves outcomes in Pax5 −/+ mice susceptible to chronic infectionZhe Lu0Olivia Stencel1Wei Liu2Eleni Vasileiou3Haifeng C Xu4Piyush Pandey5Paweł Stachura6Abdelrahman Elwy7Anastassia Tsombal8Ann-Sophie Mai9Franziska Auer10Mina N F Morcos11Maximilian Seidl12Sarah Koziel13Peter-Martin Bruch14Sascha Dietrich15Sarah Elitzur16Gunther Hartmann17Karl S Lang18Stefan Janssen19Ute Fischer20Sanil Bhatia21Philipp A Lang22Arndt Borkhardt23Julia Hauer24Aleksandra A Pandyra25Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-UniversityDepartment of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-UniversityCenter for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD)Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-UniversityDepartment of Molecular Medicine II, Medical Faculty and University Hospital, Heinrich-Heine-UniversityDepartment of Molecular Medicine II, Medical Faculty and University Hospital, Heinrich-Heine-UniversityDepartment of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-UniversityInstitute of Immunology, Medical Faculty, University of Duisburg-EssenDepartment of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-UniversityCenter for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD)Technical University of Munich, TUM School of Medicine and Health, Department of PediatricsTechnical University of Munich, TUM School of Medicine and Health, Department of PediatricsInstitute of Pathology, Medical Faculty, Heinrich-Heine-UniversityCenter for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD)Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD)Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD)Faculty of Medicine, Tel-Aviv UniversityInstitute of Clinical Chemistry and Clinical Pharmacology, University Hospital BonnInstitute of Immunology, Medical Faculty, University of Duisburg-EssenAlgorithmic Bioinformatics, Department of Biology and Chemistry, Justus Liebig UniversityDepartment of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-UniversityDepartment of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-UniversityInstitute of Immunology, Medical Faculty, University of Duisburg-EssenDepartment of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-UniversityTechnical University of Munich, TUM School of Medicine and Health, Department of PediatricsDepartment of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Center of Child and Adolescent Health, Heinrich-Heine-UniversityAbstract Viral infections pose a significant global burden. Host susceptibility to pathogens is determined by many factors including genetic variation that can lead to immunodeficient or dysregulated antiviral immune responses. Pax5 heterozygosity (Pax5 −/+), resulting in reduced PAX5 levels in mice, mimics germline or somatic PAX5 dysregulation contributing to diseases such as childhood B-cell precursor acute lymphoblastic leukemia (B-ALL). In contrast to the well-characterized roles of PAX5 during early B-cell development, little is known about how Pax5 heterozygosity impacts antiviral responses. We infected Pax5 −/+ mice with the noncytopathic Lymphocytic Choriomeningitis Virus (LCMV) and found that infection with the chronic Docile strain resulted in decreased survival of Pax5 −/+ mice. While early adaptive CD8+ T-cell (CTL) immunity was robust in Pax5 −/+ mice, LCMV-specific neutralizing antibody production was compromised leading to impaired long-term viral clearance and a pro-inflammatory milieu in the bone marrow (BM). Here we show that survival outcomes were improved upon prophylactic treatment with the β-glucan immune trainer through induction of heterologous protection against chronic infection. β-Glucan enhanced viral clearance, CTL immunity, neutralizing antibody production and reduced monocyte immunosuppression in multiple LCMV-resident host organs. New insight from this study will help design effective prophylactic treatment strategies against chronic viral infections, particularly in genetically predisposed susceptible hosts.https://doi.org/10.1038/s44321-025-00208-4Trained ImmunityChronic InfectionLCMVPAX5β-glucan |
| spellingShingle | Zhe Lu Olivia Stencel Wei Liu Eleni Vasileiou Haifeng C Xu Piyush Pandey Paweł Stachura Abdelrahman Elwy Anastassia Tsombal Ann-Sophie Mai Franziska Auer Mina N F Morcos Maximilian Seidl Sarah Koziel Peter-Martin Bruch Sascha Dietrich Sarah Elitzur Gunther Hartmann Karl S Lang Stefan Janssen Ute Fischer Sanil Bhatia Philipp A Lang Arndt Borkhardt Julia Hauer Aleksandra A Pandyra Immune training enhances anti-viral responses and improves outcomes in Pax5 −/+ mice susceptible to chronic infection EMBO Molecular Medicine Trained Immunity Chronic Infection LCMV PAX5 β-glucan |
| title | Immune training enhances anti-viral responses and improves outcomes in Pax5 −/+ mice susceptible to chronic infection |
| title_full | Immune training enhances anti-viral responses and improves outcomes in Pax5 −/+ mice susceptible to chronic infection |
| title_fullStr | Immune training enhances anti-viral responses and improves outcomes in Pax5 −/+ mice susceptible to chronic infection |
| title_full_unstemmed | Immune training enhances anti-viral responses and improves outcomes in Pax5 −/+ mice susceptible to chronic infection |
| title_short | Immune training enhances anti-viral responses and improves outcomes in Pax5 −/+ mice susceptible to chronic infection |
| title_sort | immune training enhances anti viral responses and improves outcomes in pax5 mice susceptible to chronic infection |
| topic | Trained Immunity Chronic Infection LCMV PAX5 β-glucan |
| url | https://doi.org/10.1038/s44321-025-00208-4 |
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