4.8 Article

Multi-cohort analysis of host immune response identifies conserved protective and detrimental modules associated with severity across viruses

期刊

IMMUNITY
卷 54, 期 4, 页码 753-+

出版社

CELL PRESS
DOI: 10.1016/j.immuni.2021.03.002

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资金

  1. Bill and Melinda Gates Foundation [OPP1113682]
  2. National Institute of Allergy and Infectious Diseases (NIAID) [1U19AI109662, U19AI057229, 5R01AI125197]
  3. Department of Defense [W81XWH-18-1-0253, W81XWH1910235]
  4. Ralph & Marian Falk Medical Research Trust
  5. National Science Foundation Graduate Research Fellowship
  6. Stanford Graduate Fellowship
  7. Knight-Hennessy Scholars Program
  8. Agency of Science, Technology, and Research (A*STAR), Singapore
  9. U.S. Department of Defense (DOD) [W81XWH1910235] Funding Source: U.S. Department of Defense (DOD)

向作者/读者索取更多资源

Viral infections trigger a distinct host response, with severe infections associated with increased hematopoiesis, myelopoiesis, and myeloid-derived suppressor cells. Protective and detrimental gene modules were identified to define different trajectories of outcomes, providing insights for the development of diagnostics and host-directed therapies to improve global pandemic preparedness.
Viral infections induce a conserved host response distinct from bacterial infections. We hypothesized that the conserved response is associated with disease severity and is distinct between patients with different outcomes. To test this, we integrated 4,780 blood transcriptome profiles from patients aged 0 to 90 years infected with one of 16 viruses, including SARS-CoV-2, Ebola, chikungunya, and influenza, across 34 cohorts from 18 countries, and single-cell RNA sequencing profiles of 702,970 immune cells from 289 samples across three cohorts. Severe viral infection was associated with increased hematopoiesis, myelopoiesis, and myeloid-derived suppressor cells. We identified protective and detrimental gene modules that defined distinct trajectories associated with mild versus severe outcomes. The interferon response was decoupled from the protective host response in patients with severe outcomes. These findings were consistent, irrespective of age and virus, and provide insights to accelerate the development of diagnostics and host-directed therapies to improve global pandemic preparedness.

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