Prior upregulation of interferon pathways in the nasopharynx impacts viral shedding following live attenuated influenza vaccine challenge in children.

Autor:	Costa-Martins AG; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.; Scientific Platform Pasteur, University of São Paulo, São Paulo, Brazil., Mane K; Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, P.O. Box 273, Fajara, The Gambia., Lindsey BB; The Florey Institute for Host-Pathogen Interactions and Department of Infection, Immunity and Cardiovascular Disease, The University of Sheffield, Sheffield S10 2RX, UK., Ogava RLT; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Castro Í; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Jagne YJ; Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, P.O. Box 273, Fajara, The Gambia., Sallah HJ; Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, P.O. Box 273, Fajara, The Gambia., Armitage EP; Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, P.O. Box 273, Fajara, The Gambia., Jarju S; Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, P.O. Box 273, Fajara, The Gambia., Ahadzie B; Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, P.O. Box 273, Fajara, The Gambia., Ellis-Watson R; The University of Edinburgh/MRC Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK., Tregoning JS; Department of Infectious Disease, Imperial College London, London W2 1NY, UK., Bingle CD; The Florey Institute for Host-Pathogen Interactions and Department of Infection, Immunity and Cardiovascular Disease, The University of Sheffield, Sheffield S10 2RX, UK., Bogaert D; The University of Edinburgh/MRC Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK., Clarke E; Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, P.O. Box 273, Fajara, The Gambia., Ordovas-Montanes J; Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA.; Program in Immunology, Harvard Medical School, Boston, MA 02115, USA.; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Harvard Stem Cell Institute, Cambridge, MA 02138, USA., Jeffries D; Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, P.O. Box 273, Fajara, The Gambia., Kampmann B; Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, P.O. Box 273, Fajara, The Gambia.; The Vaccine Centre, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK., Nakaya HI; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.; Scientific Platform Pasteur, University of São Paulo, São Paulo, Brazil., de Silva TI; Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, P.O. Box 273, Fajara, The Gambia.; The Florey Institute for Host-Pathogen Interactions and Department of Infection, Immunity and Cardiovascular Disease, The University of Sheffield, Sheffield S10 2RX, UK.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2021 Dec 09; Vol. 2 (12), pp. 100465. Date of Electronic Publication: 2021 Dec 09 (Print Publication: 2021).
DOI:	10.1016/j.xcrm.2021.100465
Abstrakt:	In children lacking influenza-specific adaptive immunity, upper respiratory tract innate immune responses may influence viral replication and disease outcome. We use trivalent live attenuated influenza vaccine (LAIV) as a surrogate challenge model in children aged 24-59 months to identify pre-infection mucosal transcriptomic signatures associated with subsequent viral shedding. Upregulation of interferon signaling pathways prior to LAIV is significantly associated with lower strain-specific viral loads (VLs) at days 2 and 7. Several interferon-stimulated genes are differentially expressed in children with pre-LAIV asymptomatic respiratory viral infections and negatively correlated with LAIV VLs. Upregulation of genes enriched in macrophages, neutrophils, and eosinophils is associated with lower VLs and found more commonly in children with asymptomatic viral infections. Variability in pre-infection mucosal interferon gene expression in children may impact the course of subsequent influenza infections. This variability may be due to frequent respiratory viral infections, demonstrating the potential importance of mucosal virus-virus interactions in children. Competing Interests: J.O.M. reports compensation for consulting services with Cellarity. No other conflicts of interest are reported by the authors. (© 2021 The Author(s).)
Databáze:	MEDLINE
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