Distinct post-infectious TLR2 immune remodeling in COVID-19-recovered centenarians

Area of Science:

• Immunology
• Gerontology
• Virology

Background:

• Exceptional longevity is linked to distinct immune profiles, but innate immunity post-viral infection in the oldest adults is unclear.
• Toll-like receptors (TLRs) are crucial for pathogen sensing and inflammation, including during SARS-CoV-2 infection, but their role in longevity is undefined.

Purpose of the Study:

• To investigate Toll-like receptor (TLR) gene expression in centenarians and nonagenarians who recovered from COVID-19.
• To determine if TLR expression patterns are associated with exceptional longevity and post-infectious immune responses.

Main Methods:

• Quantified TLR gene expression in peripheral blood of unvaccinated individuals who recovered from COVID-19.
• Compared TLR expression between 38 nonagenarians and 8 centenarians.
• Exploratory comparison with 10 centenarians without prior COVID-19.

Main Results:

• TLR2 was the only differentially expressed TLR gene, with lower expression in COVID-19-recovered centenarians versus nonagenarians.
• The reduced TLR2 expression in centenarians was not linked to COVID-19 severity.
• Exploratory data suggested reduced TLR2 expression reflects post-infectious immune remodeling, not just extreme aging.

Conclusions:

• Centenarians recovered from COVID-19 exhibit a distinct TLR2-associated innate immune signature.
• Exceptional longevity may be associated with specific innate immune system remodeling following SARS-CoV-2 infection.