Age-related differences in immune dynamics during SARS-CoV-2 infection in rhesus macaques
| Autor: | Emily Speranza, Jyothi N Purushotham, Julia R Port, Benjamin Schwarz, Meaghan Flagg, Brandi N Williamson, Friederike Feldmann, Manmeet Singh, Lizzette Pérez-Pérez, Gail L Sturdevant, Lydia M Roberts, Aaron Carmody, Jonathan E Schulz, Neeltje van Doremalen, Atsushi Okumura, Jamie Lovaglio, Patrick W Hanley, Carl Shaia, Ronald N Germain, Sonja M Best, Vincent J Munster, Catharine M Bosio, Emmie de Wit |
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| Rok vydání: | 2021 |
| Předmět: |
Inflammation
Aging Immunity Cellular Ecology Transcription Genetic Lymphoid Tissue SARS-CoV-2 Health Toxicology and Mutagenesis T-Lymphocytes COVID-19 Plant Science Genomics Biochemistry Genetics and Molecular Biology (miscellaneous) Macaca mulatta Models Biological Immunomodulation Gene Expression Regulation Acute Disease Antibody Formation Animals Cytokines Gene Regulatory Networks Single-Cell Analysis Bronchoalveolar Lavage Fluid Lung |
| Zdroj: | Life science alliance. 5(4) |
| ISSN: | 2575-1077 |
| Popis: | Advanced age is a key predictor of severe COVID-19. To gain insight into this relationship, we used the rhesus macaque model of SARS-CoV-2 infection. Eight older and eight younger macaques were inoculated with SARS-CoV-2. Animals were evaluated using viral RNA quantification, clinical observations, thoracic radiographs, single-cell transcriptomics, multiparameter flow cytometry, multiplex immunohistochemistry, cytokine detection, and lipidomics analysis at predefined time points in various tissues. Differences in clinical signs, pulmonary infiltrates, and virus replication were limited. Transcriptional signatures of inflammation-associated genes in bronchoalveolar lavage fluid at 3 dpi revealed efficient mounting of innate immune defenses in both cohorts. However, age-specific divergence of immune responses emerged during the post-acute phase. Older animals exhibited sustained local inflammatory innate responses, whereas local effector T-cell responses were induced earlier in the younger animals. Circulating lipid mediator and cytokine levels highlighted increased repair-associated signals in the younger animals, and persistent pro-inflammatory responses in the older animals. In summary, despite similar disease outcomes, multi-omics profiling suggests that age may delay or impair antiviral cellular immune responses and delay efficient return to immune homeostasis. |
| Databáze: | OpenAIRE |
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