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- W4313365584 abstract "Abstract Resolution of viral infections of the central nervous system (CNS) is contingent on eliciting protective immunity with minimal pathology. C57BL/6 (B6) mice elucidate efficient innate and anti-viral T cell responses which render them resistant to infection with a virulent HSV 17+ virus strain. Virus replication is limited to ganglia and brainstem. However, susceptible mice such as 129S6 and BALB/c mice harbor increased virus in the CNS. These mice show increased myeloid derived suppressor cells (MDSC) and Tregs along with associated cytokines such as G-CSF, GM-CSF, IL-10 and IL-33 resulting in reduced numbers of virus specific CD8 T cells and effector T cells with increased expression of suppressive markers such as PD-1 and LAG-3. This impaired immune response resulted in disease and mortality. Neutralization of checkpoint inhibitors or immunosuppressive cytokines and depletion of myeloid cells or Tregs did not alter susceptibility rates. However, reducing expression of IL-33 in the CNS had a beneficial effect on T cell activation and the overall outcome of disease. Intriguingly, immunizing susceptible mice with a HSV thymidine kinase mutant virus incapable of infecting CNS induced memory T cells that suppressed MDSCs and protected from a subsequent challenge with HSV 17+. Interestingly IFNg, B cells or antibody were not essential but instead revealed the importance of the T cell myeloid interaction in determining disease outcomes. IL-33 plays critical roles as an immune-modulatory Th2 cytokine regulating immune-mediated diseases and tissue function especially in the CNS and as an alarmin in response to pathogens. This study shows that tempering IL-33 responses is essential to predicting improved outcomes to CNS viral infections." @default.
- W4313365584 created "2023-01-06" @default.
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- W4313365584 date "2019-05-01" @default.
- W4313365584 modified "2023-09-26" @default.
- W4313365584 title "Impaired T cell activation resulting from IL-33 induced myeloid derived suppressor cells and IL-10 secreting Tregs is a major determinant of susceptibility to HSV1 infection of the central nervous system" @default.
- W4313365584 doi "https://doi.org/10.4049/jimmunol.202.supp.197.7" @default.
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