Age-Related Expression of IFN-λ1 <i>Versus</i> IFN-I and Beta-Defensins in the Nasopharynx of SARS-CoV-2-Infected Individuals.
Gilbert. Charly C; Lefeuvre. Caroline C; Preisser. Laurence L; Pivert. Adeline A; Soleti. Raffaella R; Blanchard. Simon S; Delneste. Yves Y; Ducancelle. Alexandra A; Couez. Dominique D; Jeannin. Pascale P
Key Findings
- Kids with COVID‑19 increase IFN‑λ1 in the nasopharynx, adults do not
- Adults (including seniors) increase IFN‑α, IFN‑β, IFN‑λ2/3, and β‑defensin 1‑3, but not IFN‑λ1
- LL‑37 levels are not changed by infection in any age group
Practical Outcomes
- There’s no direct action to take with LL‑37 based on this study. It suggests that age‑specific immune responses exist, so biohackers might focus on broader ways to support mucosal immunity rather than targeting LL‑37 specifically.
Summary
The study looked at how the nose’s immune chemicals change with age when people get COVID‑19. Kids boost a specific interferon (IFN‑λ1) while adults increase other interferons and beta‑defensins, but the antimicrobial peptide LL‑37 stays the same across ages. This shows the body’s early defenses differ by age, but it doesn’t give clear steps for using LL‑37 or other supplements.
Abstract
SARS-CoV-2 coronavirus infection induces heterogeneous symptoms, ranging from asymptomatic to lethal forms. Severe forms usually occur in the elderly and/or individuals with comorbidities. Children generally remain asymptomatic to primary infection, suggesting that they may have an effective local innate immune response. IFN-I and -III have non-redundant protective roles against SARS-CoV-2, although sometimes damaging the host. The expression and role of anti-viral peptides during SARS-CoV-2 infection have thus far been little studied. We aimed to identify the innate immune molecules present at the SARS-CoV-2 entry point. We analyzed the mRNA levels of type I (IFN-α and -β) and type III (IFN-λ1-3) interferons and selected antiviral peptides (<i>i.e.</i>, β-defensins 1-3, α-defensins [HNP1-3, HD5] pentraxin-3, surfactant protein D, the cathelicidin LL-37 and interleukin-26) in nasopharyngeal swabs from 226 individuals of various ages, either infected with SARS-CoV-2 (symptomatic or asymptomatic) or negative for the virus. We observed that infection induced selective upregulation of IFN-λ1 expression in pediatric subjects (≤15 years), whereas IFN-α, IFN-β, IFN-λ2/λ3, and β-defensin 1-3 expression was unaffected. Conversely, infection triggered upregulation of IFN-α, IFN-β, IFN-λ2/λ3, and β-defensin 1-3 mRNA expression in adults (15-65 years) and the elderly (≥ 65 years), but without modulation of IFN-λ1. The expression of these innate molecules was not associated with gender or symptoms. Expression of the interferon-stimulated genes IFITM1 and IFITM3 was upregulated in SARS-CoV-2-positive subjects and reached similar levels in the three age groups. Finally, age-related differences in nasopharyngeal innate immunity were also observed in SARS-CoV-2-negative subjects. This study shows that the expression patterns of IFN-I/-III and certain anti-viral molecules in the nasopharyngeal mucosa of SARS-CoV-2-infected subjects differ with age and suggests that susceptibility to SARS-CoV-2 may be related to intrinsic differences in the nature of mucosal anti-viral innate immunity.
Study Information
pubmed
2021
2021-11-10T00:00:00.000Z
10.3389/fimmu.2021.750279
26
73