Age-Related Expression of IFN-λ1 Versus IFN-I and Beta-Defensins in the Nasopharynx of SARS-CoV-2-Infected Individuals
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 i...
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2021
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oai:doaj.org-article:3d193135ed754206b2cbaf5704f1afa12021-11-10T07:56:08ZAge-Related Expression of IFN-λ1 Versus IFN-I and Beta-Defensins in the Nasopharynx of SARS-CoV-2-Infected Individuals1664-322410.3389/fimmu.2021.750279https://doaj.org/article/3d193135ed754206b2cbaf5704f1afa12021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.750279/fullhttps://doaj.org/toc/1664-3224SARS-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.Charly GilbertCharly GilbertCaroline LefeuvreCaroline LefeuvreLaurence PreisserAdeline PivertAdeline PivertRaffaella SoletiSimon BlanchardSimon BlanchardYves DelnesteYves DelnesteAlexandra DucancelleAlexandra DucancelleDominique CouezPascale JeanninPascale JeanninFrontiers Media S.A.articleIFN - interferondefensinnasopharyngeal mucosaSARS – CoV – 2COVID - 19ageingImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
IFN - interferon defensin nasopharyngeal mucosa SARS – CoV – 2 COVID - 19 ageing Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
IFN - interferon defensin nasopharyngeal mucosa SARS – CoV – 2 COVID - 19 ageing Immunologic diseases. Allergy RC581-607 Charly Gilbert Charly Gilbert Caroline Lefeuvre Caroline Lefeuvre Laurence Preisser Adeline Pivert Adeline Pivert Raffaella Soleti Simon Blanchard Simon Blanchard Yves Delneste Yves Delneste Alexandra Ducancelle Alexandra Ducancelle Dominique Couez Pascale Jeannin Pascale Jeannin Age-Related Expression of IFN-λ1 Versus IFN-I and Beta-Defensins in the Nasopharynx of SARS-CoV-2-Infected Individuals |
| description |
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. |
| format |
article |
| author |
Charly Gilbert Charly Gilbert Caroline Lefeuvre Caroline Lefeuvre Laurence Preisser Adeline Pivert Adeline Pivert Raffaella Soleti Simon Blanchard Simon Blanchard Yves Delneste Yves Delneste Alexandra Ducancelle Alexandra Ducancelle Dominique Couez Pascale Jeannin Pascale Jeannin |
| author_facet |
Charly Gilbert Charly Gilbert Caroline Lefeuvre Caroline Lefeuvre Laurence Preisser Adeline Pivert Adeline Pivert Raffaella Soleti Simon Blanchard Simon Blanchard Yves Delneste Yves Delneste Alexandra Ducancelle Alexandra Ducancelle Dominique Couez Pascale Jeannin Pascale Jeannin |
| author_sort |
Charly Gilbert |
| title |
Age-Related Expression of IFN-λ1 Versus IFN-I and Beta-Defensins in the Nasopharynx of SARS-CoV-2-Infected Individuals |
| title_short |
Age-Related Expression of IFN-λ1 Versus IFN-I and Beta-Defensins in the Nasopharynx of SARS-CoV-2-Infected Individuals |
| title_full |
Age-Related Expression of IFN-λ1 Versus IFN-I and Beta-Defensins in the Nasopharynx of SARS-CoV-2-Infected Individuals |
| title_fullStr |
Age-Related Expression of IFN-λ1 Versus IFN-I and Beta-Defensins in the Nasopharynx of SARS-CoV-2-Infected Individuals |
| title_full_unstemmed |
Age-Related Expression of IFN-λ1 Versus IFN-I and Beta-Defensins in the Nasopharynx of SARS-CoV-2-Infected Individuals |
| title_sort |
age-related expression of ifn-λ1 versus ifn-i and beta-defensins in the nasopharynx of sars-cov-2-infected individuals |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/3d193135ed754206b2cbaf5704f1afa1 |
| work_keys_str_mv |
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