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Imaging of In Situ Interferon Gamma Production in the Mouse Spleen following Listeria monocytogenes Infection
Published on: July 16, 2019
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Sepsis Impairs IFN-γ Production in CD8 T Cells through Changes in Local Chromatin Landscape
J Alejandro Cisneros-Segura1,2, Noé Rodríguez-Rodríguez1,3, Adrián Albarrán-Godínez1,4
1Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Journal of Immunology (Baltimore, Md. : 1950)
|July 22, 2024
Summary
Sepsis survivors experience lingering immune issues. This study reveals sepsis causes intrinsic CD8 T cell defects, impairing their ability to fight infections by reducing IFN-γ production and altering epigenetic regulation.
Area of Science:
- Immunology
- Infectious Diseases
- Cellular Biology
Background:
- Sepsis involves widespread inflammation and immune system dysregulation.
- Persistent immune dysfunction in sepsis survivors increases susceptibility to secondary infections.
- CD8 T cell dysfunction is a key factor in the immunosuppression observed in sepsis survivors.
Purpose of the Study:
- To investigate intrinsic defects in CD8 T cells caused by sepsis.
- To analyze how sepsis exposure impacts CD8 T cell function and epigenetic regulation.
- To establish an animal model for studying sepsis-induced CD8 T cell impairment.
Main Methods:
- Adoptive transfer of CD8 OT-I T cells into mice subjected to cecal ligation and puncture to induce sepsis.
- Isolation and functional assessment of sepsis-exposed CD8 T cells in secondary recipient mice challenged with Listeria monocytogenes.
- Analysis of gene and epigenetic marker expression (IFN-γ, Ifng-as1, histone modifications) in CD8 T cells.
Main Results:
- Sepsis-exposed CD8 T cells conferred reduced protection against Listeria monocytogenes infection in naive recipients.
- These cells exhibited decreased Interferon-gamma (IFN-γ) production but retained activation, expansion, and cytotoxic potential.
- Lower transcript levels of IFN-γ and Ifng-as1, along with reduced active promoter histone modifications, were observed in sepsis-exposed CD8 T cells.
Conclusions:
- Sepsis induces intrinsic defects in CD8 T cells, specifically impairing their IFN-γ production.
- Epigenetic alterations, including reduced Ifng-as1 and specific histone modifications, contribute to sepsis-induced CD8 T cell dysfunction.
- Understanding these intrinsic defects is crucial for developing strategies to improve immune recovery after sepsis.
