Serum Cytokines Predict Neurological Damage in Genetically Diverse Mouse Models
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Published on: May 27, 2022
Aracely A Pérez Gómez1,2, Moumita Karmakar3, Raymond J Carroll3
1Interdisciplinary Faculty of Toxicology, College of Veterinary Medicine and Biomedical Sciences, Texas A & M University, College Station, TX 77843, USA.
Abstract:
Viral infections contribute to neurological and immunological dysfunction driven by complex genetic networks. Theiler's murine encephalomyelitis virus (TMEV) causes neurological dysfunction in mice and can model human outcomes to viral infections. Here, we used genetically distinct mice from five Collaborative Cross mouse strains and C57BL/6J to demonstrate how TMEV-induced immune responses in serum may predict neurological outcomes in acute infection. To test the hypothesis that serum cytokine levels can provide biomarkers for phenotypic outcomes of acute disease, we compared cytokine levels at pre-injection, 4 days post-injection (d.p.i.), and 14 d.p.i. Each strain produced unique baseline cytokine levels and had distinct immune responses to the injection procedure itself. Thus, we eliminated the baseline responses to the injection procedure itself and identified cytokines and chemokines induced specifically by TMEV infection. Then, we identified strain-specific longitudinal cytokine profiles in serum during acute disease. Using stepwise regression analysis, we identified serum immune markers predictive for TMEV-induced neurological phenotypes of the acute phase, e.g., IL-9 for limb paralysis; and TNF-α, IL-1β, and MIP-1β for limb weakness. These findings indicate how temporal differences in immune responses are influenced by host genetic background and demonstrate the potential of serum biomarkers to track the neurological effects of viral infection.
Insights
Viral infections can cause neurological issues. This study found specific serum immune markers, like IL-9 and TNF-α, can predict neurological dysfunction in mice infected with Theiler
Area of Science:
- Neuroimmunology
- Virology
- Genetics
Background:
- Viral infections can lead to complex neurological and immunological dysfunction.
- Theiler's murine encephalomyelitis virus (TMEV) in mice serves as a model for human viral infections.
- Host genetics significantly influence immune responses and disease outcomes.
Purpose of the Study:
- To investigate if serum cytokine levels can serve as biomarkers for neurological outcomes in TMEV-infected mice.
- To identify specific immune markers that predict neurological dysfunction during acute viral infection.
- To understand the role of host genetic background in TMEV-induced immune responses.
Main Methods:
- Utilized genetically distinct Collaborative Cross mouse strains and C57BL/6J mice.
- Measured serum cytokine and chemokine levels at pre-injection, 4 days post-injection (d.p.i.), and 14 d.p.i.
- Employed stepwise regression analysis to identify predictive immune markers for neurological phenotypes.
Main Results:
- Identified unique baseline cytokine levels and distinct responses to the injection procedure among different mouse strains.
- Determined strain-specific longitudinal cytokine profiles induced specifically by TMEV infection.
- Identified serum immune markers predicting neurological phenotypes: IL-9 for limb paralysis; TNF-α, IL-1β, and MIP-1β for limb weakness.
Conclusions:
- Serum immune markers can predict neurological dysfunction in TMEV-infected mice.
- Temporal immune responses are influenced by host genetic background.
- Serum biomarkers show potential for tracking neurological effects of viral infections.
