학술논문
Differential anti-viral response to respiratory syncytial virus A in preterm and term infants.
Document Type
Academic Journal
Author
Anderson J; Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia. Electronic address: jeremy.anderson@mcri.edu.au.; Imran S; Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia.; Ng YY; Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia.; Wang T; Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia.; Ashley S; Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia.; Minh Thang C; Pasteur Institute of Ho Chi Minh City, Vietnam.; Quang Thanh L; Tu Du Hospital, Ho Chi Minh City, Vietnam.; Thi Trang Dai V; Pasteur Institute of Ho Chi Minh City, Vietnam.; Van Thanh P; Pasteur Institute of Ho Chi Minh City, Vietnam.; Thi Hong Nhu B; Tu Du Hospital, Ho Chi Minh City, Vietnam.; Ngoc Xuan Trang D; Tu Du Hospital, Ho Chi Minh City, Vietnam.; Thi Phuong Trinh P; Tu Du Hospital, Ho Chi Minh City, Vietnam.; Thanh Binh L; Tu Du Hospital, Ho Chi Minh City, Vietnam.; Thuong Vu N; Tu Du Hospital, Ho Chi Minh City, Vietnam.; Trong Toan N; Tu Du Hospital, Ho Chi Minh City, Vietnam.; Novakovic B; Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia.; Tang MLK; Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; Allergy and Lung Health Unit, University of Melbourne, Melbourne, Australia.; Wurzel D; Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; Allergy and Lung Health Unit, University of Melbourne, Melbourne, Australia; Royal Children's Hospital, Melbourne, Australia.; Mulholland K; Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; London School of Hygiene and Tropical Medicine, London, United Kingdom.; Pellicci DG; Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia.; Do LAH; Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia. Electronic address: lienanhha.do@mcri.edu.au.; Licciardi PV; Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia. Electronic address: paul.licciardi@mcri.edu.au.
Source
Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101647039 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2352-3964 (Electronic) Linking ISSN: 23523964 NLM ISO Abbreviation: EBioMedicine Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Preterm infants are more likely to experience severe respiratory syncytial virus (RSV) disease compared to term infants. The reasons for this are multi-factorial, however their immature immune system is believed to be a major contributing factor.
Methods: We collected cord blood from 25 preterm (gestational age 30.4-34.1 weeks) and 25 term infants (gestation age 37-40 weeks) and compared the response of cord blood mononuclear cells (CBMCs) to RSVA and RSVB stimulation using neutralising assays, high-dimensional flow cytometry, multiplex cytokine assays and RNA-sequencing.
Findings: We found that preterm and term infants had similar maternally derived neutralising antibody titres to RSVA and RSVB. Preterm infants had significantly higher myeloid dendritic cells (mDC) RSV infection compared to term infants. Differential gene expression analysis of RSVA stimulated CBMCs revealed enrichment of genes involved in cytokine production and immune regulatory pathways involving IL-10, IL-36γ, CXCL1, CXCL2, SOCS1 and SOCS3 in term infants, while differentially expressed genes (DEGs) in preterm infants were related to cell cycle (CDK1, TTK, ESCO2, KNL1, CDC25A, MAD2L1) without associated expression of immune response genes. Furthermore, enriched genes in term infants were highly correlated suggesting an increased co-ordination of their immune response to RSVA. When comparing DEGs in preterm and term infants following RSVB stimulation, no differences in immune response genes were identified.
Interpretation: Overall, our data suggests that preterm infants have a more restricted immunological response to RSVA compared with term infants. While further studies are required, these findings may help to explain why preterm infants are more susceptible to severe RSV disease and identify potential therapeutic targets to protect these vulnerable infants.
Funding: Murdoch Children's Research Institute Infection and Immunity theme grant.
Competing Interests: Declaration of interests D.W receives funds from GSK to lead a study evaluating RSV testing in Australia. Payments are made to research funds. D.W also receives consultancy funds from Sanofi, MSD and Praxhub which are paid to research funds. D. W is a co-chair on TSANZ and a working group member of Therapeutic Guidelines Ltd, (Antibiotics, respiratory) Australian clinical guidelines. L.A.H.D receives grants from CEPI, PATH and BMGF where payments are made to the institution. P.V.L receives grants from CEPI where payments are made to the institution. M.L.K.T receives grants from NHMRC and Allergy and Immunology Foundation of Australasia. M.L.K.T receives royalties from the book “Food Allergies for Dummies”, and consultancy fees from the Abrocitinib advisory board of Pfizer. M.L.K.T has received flight support from APAAACI Congress and the CUHK Allergy conference. M.L.K.T has patents covering food allergy and pending patents from allergy treatments. M.L.K.T is the board director for AllergyPal, on the board of directors for APAAACI and an advisory board membership for AAA which are all unpaid. M.L.K.T has received probiotics from Metagenics for the PEAT study and is a CFAR3 investigator, associate editor for JACI global and on the editorial board of World Allergy Organisation Journal, Asia Pacific Allergy Journal and JACI In Practice. K.M received funding support from the BMGF, funding paid to the institute and is a member of the WHO SAGE committee. K.M is also an investigator on a observational study of adult pneumonia in Mongolia funded by Pfizer. K.M has received funding support to attend meetings by the WHO and Christian Medical College Vellore India. K.M has also participated on the data safety monitoring board of Novavax COVID-19 studies in an unpaid position.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Methods: We collected cord blood from 25 preterm (gestational age 30.4-34.1 weeks) and 25 term infants (gestation age 37-40 weeks) and compared the response of cord blood mononuclear cells (CBMCs) to RSVA and RSVB stimulation using neutralising assays, high-dimensional flow cytometry, multiplex cytokine assays and RNA-sequencing.
Findings: We found that preterm and term infants had similar maternally derived neutralising antibody titres to RSVA and RSVB. Preterm infants had significantly higher myeloid dendritic cells (mDC) RSV infection compared to term infants. Differential gene expression analysis of RSVA stimulated CBMCs revealed enrichment of genes involved in cytokine production and immune regulatory pathways involving IL-10, IL-36γ, CXCL1, CXCL2, SOCS1 and SOCS3 in term infants, while differentially expressed genes (DEGs) in preterm infants were related to cell cycle (CDK1, TTK, ESCO2, KNL1, CDC25A, MAD2L1) without associated expression of immune response genes. Furthermore, enriched genes in term infants were highly correlated suggesting an increased co-ordination of their immune response to RSVA. When comparing DEGs in preterm and term infants following RSVB stimulation, no differences in immune response genes were identified.
Interpretation: Overall, our data suggests that preterm infants have a more restricted immunological response to RSVA compared with term infants. While further studies are required, these findings may help to explain why preterm infants are more susceptible to severe RSV disease and identify potential therapeutic targets to protect these vulnerable infants.
Funding: Murdoch Children's Research Institute Infection and Immunity theme grant.
Competing Interests: Declaration of interests D.W receives funds from GSK to lead a study evaluating RSV testing in Australia. Payments are made to research funds. D.W also receives consultancy funds from Sanofi, MSD and Praxhub which are paid to research funds. D. W is a co-chair on TSANZ and a working group member of Therapeutic Guidelines Ltd, (Antibiotics, respiratory) Australian clinical guidelines. L.A.H.D receives grants from CEPI, PATH and BMGF where payments are made to the institution. P.V.L receives grants from CEPI where payments are made to the institution. M.L.K.T receives grants from NHMRC and Allergy and Immunology Foundation of Australasia. M.L.K.T receives royalties from the book “Food Allergies for Dummies”, and consultancy fees from the Abrocitinib advisory board of Pfizer. M.L.K.T has received flight support from APAAACI Congress and the CUHK Allergy conference. M.L.K.T has patents covering food allergy and pending patents from allergy treatments. M.L.K.T is the board director for AllergyPal, on the board of directors for APAAACI and an advisory board membership for AAA which are all unpaid. M.L.K.T has received probiotics from Metagenics for the PEAT study and is a CFAR3 investigator, associate editor for JACI global and on the editorial board of World Allergy Organisation Journal, Asia Pacific Allergy Journal and JACI In Practice. K.M received funding support from the BMGF, funding paid to the institute and is a member of the WHO SAGE committee. K.M is also an investigator on a observational study of adult pneumonia in Mongolia funded by Pfizer. K.M has received funding support to attend meetings by the WHO and Christian Medical College Vellore India. K.M has also participated on the data safety monitoring board of Novavax COVID-19 studies in an unpaid position.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)