%0 Journal Article
%A Lu, Zhe
%A Stencel, Olivia
%A Liu, Wei
%A Vasileiou, Eleni
%A Xu, Haifeng C
%A Pandey, Piyush
%A Stachura, Paweł
%A Elwy, Abdelrahman
%A Tsombal, Anastassia
%A Mai, Ann-Sophie
%A Auer, Franziska
%A Morcos, Mina N F
%A Seidl, Maximilian
%A Koziel, Sarah
%A Bruch, Peter-Martin
%A Dietrich, Sascha
%A Elitzur, Sarah
%A Hartmann, Gunther
%A Lang, Karl S
%A Janssen, Stefan
%A Fischer, Ute
%A Bhatia, Sanil
%A Lang, Philipp A
%A Borkhardt, Arndt
%A Hauer, Julia
%A Pandyra, Aleksandra A
%T Immune training enhances anti-viral responses and improves outcomes in Pax5-/+ mice susceptible to chronic infection.
%J EMBO molecular medicine
%V 17
%N 4
%@ 1757-4676
%C [London]
%I Nature Publishing Group UK
%M DKFZ-2025-00566
%P 696-721
%D 2025
%Z 2025 Apr;17(4):696-721
%X 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.
%K Chronic Infection (Other)
%K LCMV (Other)
%K PAX5 (Other)
%K Trained Immunity (Other)
%K β-glucan (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40082582
%R 10.1038/s44321-025-00208-4
%U https://inrepo02.dkfz.de/record/299829