Profiling system-wide immune signaling in chronic viral infection and its response to viral clearance

Autor: Cesar Joel Lopez Angel, David Furman, Edward Pham, Benjamin Fram, Thai Nguyen, Aijaz Ahmed, Philip Grant, Holden T Maecker, Jeffrey Glenn, Mark M Davis
Rok vydání: 2016
Předmět:
Zdroj: The Journal of Immunology. 196:79.3-79.3
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.196.supp.79.3
Popis: There are many billions of chronic viral infections in humans, as each of the ~7.4 billion individuals alive today each host ~10 chronic infections. The clinical significance of these infections vary widely, yet all individuals with chronic viral infections rely on persistent antiviral immunity to keep these infections in check. Over time, chronically infected individuals exhibit impaired immune function as evidenced by their poor response to vaccination and progressive T cell dysfunction – a process known as exhaustion. The impact of chronic viral infection on other immune cell types is understudied, and whether the immune landscape can be restored upon viral eradication is unknown. To address these questions, we have prospectively recruited a cohort of HCV-infected patients who underwent standard of care treatment leading to viral clearance in 12 weeks, a cohort of virologically suppressed HIV-infected patients, and an aged-matched cohort of healthy individuals. With the use of single-cell mass cytometry (CyTOF) and systems bioinformatics analyses, we comprehensively characterized the molecular pathways and functional signature underlying immune exhaustion. Here we report an immune signaling signature that differentiates individuals with chronic viral infections from uninfected individuals. While this signature is largely unaltered following viral clearance, we identified a set of functional parameters that are restorable upon successful viral eradication which represent a previously unobserved level of plasticity of the human immune system.
Databáze: OpenAIRE
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