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<p>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. <i>Pax5</i> heterozygosity (<i>Pax5</i><sup>−/+</sup>), 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 <i>Pax5</i> heterozygosity impacts antiviral responses. We infected <i>Pax5</i><sup>−/+</sup> mice with the noncytopathic Lymphocytic Choriomeningitis Virus (LCMV) and found that infection with the chronic Docile strain resulted in decreased survival of <i>Pax5</i><sup>−/+</sup> mice. While early adaptive CD8<sup>+</sup> T-cell (CTL) immunity was robust in <i>Pax5</i><sup>−/+</sup> 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.</p>

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Immune training enhances anti-viral responses and improves outcomes in Pax5−/+ mice susceptible to chronic infection

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月13日

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  • 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

摘要

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.