Τίτλος:
Differential maturation trajectories of innate antiviral immunity in health and atopy
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background: The maturation of innate immune responses in health and atopy is still incompletely understood. Methods: We aimed to evaluate age-related trajectories of the TLR3 and TLR7/8 pathways from birth to adulthood and whether these differ between healthy and atopic individuals. Peripheral blood mononuclear cells (PBMCs) were isolated from 39 otherwise healthy, atopic and 39 non-atopic subjects, aged 0–45 years. Selected cytokines involved in antiviral responses were measured by Luminex in culture supernatants of poly(I:C)- and R848-stimulated PBMCs. The non-parametric correlation between age and cytokine expression and differences in developmental trajectories between healthy and atopic subjects were estimated. Patterns of cytokine development were identified with principal component analysis. Results: Normal innate immune maturation entails significant and progressive age-related changes in the production of IL-1β, TNF-α, MIP-1β, MCP-3, IP-10, IL-10, IL-12p70, and IFN-γ upon TLR3 and/or TLR7/8 stimulation. Individual cytokines made small contributions to the observed variability; chemokines MCP-3 and IP-10 were key contributors. The development of these pathways deviated in atopic subjects with significant differences observed in the trajectories of IL-1β, MIP-1β, and IL-10 syntheses. Conclusion: TLR3 and TLR7/8 pathways mature during childhood, while atopy is associated with an abnormal maturation pattern. Suboptimal responses in Th1, inflammatory cytokine, and chemokine production may be implicated in poor antiviral immunity in atopics. Moreover, the deficient maturation of IL-10 synthesis may be implicated in the breaking of tolerance, characterizing the onset of atopic disease. © 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
Συγγραφείς:
Georgountzou, A.
Kokkinou, D.
Taka, S.
Maggina, P.
Lakoumentas, J.
Papaevangelou, V.
Tsolia, M.
Xepapadaki, P.
Andreakos, E.
Papadopoulos, N.G.
Περιοδικό:
Pediatric Allergy and Immunology
Εκδότης:
John Wiley and Sons Inc
Λέξεις-κλειδιά:
allergen; chemokine; cytokine; gamma interferon; gamma interferon inducible protein 10; interleukin 10; interleukin 12p70; macrophage inflammatory protein 1beta; monocyte chemotactic protein 3; polyinosinic polycytidylic acid; resiquimod; toll like receptor 3; toll like receptor 7; toll like receptor 8; tumor necrosis factor; antivirus agent; chemokine; cytokine, adolescent; adult; adulthood; age; Article; atopy; birth; cell culture; child; childhood; clinical article; controlled study; correlation analysis; cross-sectional study; cytokine production; evaluation study; female; human; human cell; infant; inflammation; innate immunity; male; newborn; peripheral blood mononuclear cell; postnatal development; principal component analysis; protein expression; protein synthesis; supernatant; Th1 cell; virus immunity; innate immunity; mononuclear cell, Adult; Antiviral Agents; Chemokines; Cytokines; Humans; Immunity, Innate; Leukocytes, Mononuclear
