Shared signatures of immune dysfunction in chronic inflammatory states revealed by system-wide immune monitoring
Abstract/Contents
- Abstract
- Chronic inflammation is thought to be a major cause of morbidity and mortality in aging, but whether similar mechanisms underlie dysfunction in infection-associated chron-ic inflammation is unclear. Here we profiled the immune proteome, and cellular composi-tion and signaling states in a cohort of aging individuals versus a set of human immunode-ficiency virus (HIV) patients on long term ART therapy or hepatitis C virus (HCV) pa-tients before and after sofosbuvir treatment. We found shared alterations in aging- and infection-associated chronic inflammation including T cell memory inflation, upregulation of intracellular signaling pathways of inflammation, and diminished sensitivity to cyto-kines in lymphocytes and myeloid cells. In the HIV cohort, these dysregulations were evi-dent despite viral suppression for over ten years. Viral clearance in the HCV cohort par-tially restored cellular sensitivity to interferon (IFN)-α, but many immune system altera-tions persisted for at least one year post-treatment. Our findings indicate that in the HIV and HCV cohorts a broad remodeling and degradation of the immune system can persist for a year or more, even after the removal or drastic reduction of the pathogen load and that this shares some features of chronic inflammation in aging.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | López Angel, César Joel |
|---|---|
| Degree supervisor | Davis, Mark M |
| Thesis advisor | Davis, Mark M |
| Thesis advisor | Glenn, Jeffrey S, 1962- |
| Thesis advisor | Khatri, Purvesh |
| Thesis advisor | Maecker, Holden |
| Degree committee member | Glenn, Jeffrey S, 1962- |
| Degree committee member | Khatri, Purvesh |
| Degree committee member | Maecker, Holden |
| Associated with | Stanford University, Program in Immunology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | César J. López Angel. |
|---|---|
| Note | Submitted to the Program in Immunology. |
| Thesis | Thesis Ph.D. Stanford University 2020. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Cesar Joel Lopez Angel
- License
- This work is licensed under a Creative Commons Attribution 3.0 Unported license (CC BY).
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