TY  - JOUR
AU  - Lu, Zhe
AU  - Stencel, Olivia
AU  - Liu, Wei
AU  - Vasileiou, Eleni
AU  - Xu, Haifeng C
AU  - Pandey, Piyush
AU  - Stachura, Paweł
AU  - Elwy, Abdelrahman
AU  - Tsombal, Anastassia
AU  - Mai, Ann-Sophie
AU  - Auer, Franziska
AU  - Morcos, Mina N F
AU  - Seidl, Maximilian
AU  - Koziel, Sarah
AU  - Bruch, Peter-Martin
AU  - Dietrich, Sascha
AU  - Elitzur, Sarah
AU  - Hartmann, Gunther
AU  - Lang, Karl S
AU  - Janssen, Stefan
AU  - Fischer, Ute
AU  - Bhatia, Sanil
AU  - Lang, Philipp A
AU  - Borkhardt, Arndt
AU  - Hauer, Julia
AU  - Pandyra, Aleksandra A
TI  - Immune training enhances anti-viral responses and improves outcomes in Pax5-/+ mice susceptible to chronic infection.
JO  - EMBO molecular medicine
VL  - 17
IS  - 4
SN  - 1757-4676
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2025-00566
SP  - 696-721
PY  - 2025
N1  - 2025 Apr;17(4):696-721
AB  - 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.
KW  - Chronic Infection (Other)
KW  - LCMV (Other)
KW  - PAX5 (Other)
KW  - Trained Immunity (Other)
KW  - β-glucan (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40082582
DO  - DOI:10.1038/s44321-025-00208-4
UR  - https://inrepo02.dkfz.de/record/299829
ER  -