Age-Related Expression of IFN-λ1 Versus IFN-I and Beta-Defensins in the Nasopharynx of SARS-CoV-2-Infected Individuals

• Published in: Frontiers in immunology Vol. 12; p. 750279
• Main Authors: Gilbert, Charly, Lefeuvre, Caroline, Preisser, Laurence, Pivert, Adeline, Soleti, Raffaella, Blanchard, Simon, Delneste, Yves, Ducancelle, Alexandra, Couez, Dominique, Jeannin, Pascale
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers 10.11.2021; Frontiers Media S.A
• Subjects: Adolescent; Adult; Age Factors; Aged; ageing; Antiviral Restriction Factors - analysis; beta-Defensins - biosynthesis; beta-Defensins - immunology; Cells, Cultured; COVID - 19; COVID-19 - immunology; defensin; Emerging diseases; Female; Human health and pathology; Humans; IFN - interferon; Immunity, Innate - immunology; Immunology; Infectious diseases; Innate immunity; Interferon Lambda; Interferon Type I - biosynthesis; Interferon Type I - immunology; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; Interferons - biosynthesis; Interferons - immunology; Interleukins - biosynthesis; Interleukins - immunology; Life Sciences; Male; Microbiology and Parasitology; Middle Aged; Nasal Mucosa - immunology; nasopharyngeal mucosa; Nasopharynx - immunology; Pulmonology and respiratory tract; SARS – CoV – 2; SARS-CoV-2 - immunology; Virology; Young Adult; SARS – CoV – 2; COVID - 19; ageing; defensin; nasopharyngeal mucosa; IFN - interferon; mucosal immunity; IFN; COVID- 19; interferon; SARS– CoV– 2
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.750279

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.e. , 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.