Impaired Cytokine Secretion Contributes to Age-Dependent Immune Dysfunction in SARS Coronavirus Response and Is Restored by Young CD11b-Positive Cell Transfer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40583123.
- Also identified by DOI 10.1111/acel.70154 and PMC identifier 12419839.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
COVID-19 mortality disproportionately affects the elderly, yet the cellular and molecular factors contributing to age-related immune system remodeling remain unclear. Using SARS-CoV-derived ssRNA sequences, we modeled age-dependent immune responses in mice. Aged mice exhibited higher mortality and severe lung inflammation upon viral ssRNA challenge, mirroring clinical observations. We uncovered a pre-existing inflammatory state in aged mice, characterized by elevated baseline levels of specific immune cells and cytokines correlating with poor outcomes. Age-related immune dysfunction stemmed from impaired IRF7 signaling and defective SNARE-mediated cytokine secretion in CD11b<sup>+</sup> cells. Notably, the adoptive transfer of young CD11b<sup>+</sup> cells to aged mice exposed to SARS-CoV2 ssRNA reduced mortality, alleviated lung inflammation, and normalized cytokine profiles. These findings provide insights into age-related immune dysregulation during viral challenges and suggest potential therapeutic strategies for severe COVID-19 in the elderly.
Medical subject headings
- COVID-19
- Cytokines
- SARS-CoV-2
- CD11b Antigen
- Aging
- Adoptive Transfer