Haemophilus is overrepresented in the nasopharynx of infants hospitalized with RSV infection and associated with increased viral load and enhanced mucosal CXCL8 responses

Abstract Background While almost all infants are infected with respiratory syncytial virus (RSV) before the age of 2 years, only a small percentage develops severe disease. Previous studies suggest that the nasopharyngeal microbiome affects disease development. We therefore studied the effect of the...

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Main Authors: Thomas H. A. Ederveen, Gerben Ferwerda, Inge M. Ahout, Marloes Vissers, Ronald de Groot, Jos Boekhorst, Harro M. Timmerman, Martijn A. Huynen, Sacha A. F. T. van Hijum, Marien I. de Jonge
Format: Article
Language:English
Published: BMC 2018-01-01
Series:Microbiome
Subjects:
Online Access:http://link.springer.com/article/10.1186/s40168-017-0395-y
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author Thomas H. A. Ederveen
Gerben Ferwerda
Inge M. Ahout
Marloes Vissers
Ronald de Groot
Jos Boekhorst
Harro M. Timmerman
Martijn A. Huynen
Sacha A. F. T. van Hijum
Marien I. de Jonge
author_facet Thomas H. A. Ederveen
Gerben Ferwerda
Inge M. Ahout
Marloes Vissers
Ronald de Groot
Jos Boekhorst
Harro M. Timmerman
Martijn A. Huynen
Sacha A. F. T. van Hijum
Marien I. de Jonge
author_sort Thomas H. A. Ederveen
collection DOAJ
description Abstract Background While almost all infants are infected with respiratory syncytial virus (RSV) before the age of 2 years, only a small percentage develops severe disease. Previous studies suggest that the nasopharyngeal microbiome affects disease development. We therefore studied the effect of the nasopharyngeal microbiome on viral load and mucosal cytokine responses, two important factors influencing the pathophysiology of RSV disease. To determine the relation between (i) the microbiome of the upper respiratory tract, (ii) viral load, and (iii) host mucosal inflammation during an RSV infection, nasopharyngeal microbiota profiles of RSV infected infants (< 6 months) with different levels of disease severity and age-matched healthy controls were determined by 16S rRNA marker gene sequencing. The viral load was measured using qPCR. Nasopharyngeal CCL5, CXCL10, MMP9, IL6, and CXCL8 levels were determined with ELISA. Results Viral load in nasopharyngeal aspirates of patients associates significantly to total nasopharyngeal microbiota composition. Healthy infants (n = 21) and RSV patients (n = 54) display very distinct microbial patterns, primarily characterized by a loss in commensals like Veillonella and overrepresentation of opportunistic organisms like Haemophilus and Achromobacter in RSV-infected individuals. Furthermore, nasopharyngeal microbiota profiles are significantly different based on CXCL8 levels. CXCL8 is a chemokine that was previously found to be indicative for disease severity and for which we find Haemophilus abundance as the strongest predictor for CXCL8 levels. Conclusions The nasopharyngeal microbiota in young infants with RSV infection is marked by an overrepresentation of the genus Haemophilus. We present that this bacterium is associated with viral load and mucosal CXCL8 responses, both which are involved in RSV disease pathogenesis.
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spelling doaj.art-c877b3a9af3941fdb785b57659ce462f2022-12-22T03:50:55ZengBMCMicrobiome2049-26182018-01-016111310.1186/s40168-017-0395-yHaemophilus is overrepresented in the nasopharynx of infants hospitalized with RSV infection and associated with increased viral load and enhanced mucosal CXCL8 responsesThomas H. A. Ederveen0Gerben Ferwerda1Inge M. Ahout2Marloes Vissers3Ronald de Groot4Jos Boekhorst5Harro M. Timmerman6Martijn A. Huynen7Sacha A. F. T. van Hijum8Marien I. de Jonge9Center for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical CenterLaboratory of Pediatric Infectious Diseases, Radboud Center for Infectious Diseases, Radboud University Medical CenterLaboratory of Pediatric Infectious Diseases, Radboud Center for Infectious Diseases, Radboud University Medical CenterCentre for Infectious Disease Control, National Institute for Public Health and the EnvironmentLaboratory of Pediatric Infectious Diseases, Radboud Center for Infectious Diseases, Radboud University Medical CenterCenter for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical CenterNIZOCenter for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical CenterCenter for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical CenterLaboratory of Pediatric Infectious Diseases, Radboud Center for Infectious Diseases, Radboud University Medical CenterAbstract Background While almost all infants are infected with respiratory syncytial virus (RSV) before the age of 2 years, only a small percentage develops severe disease. Previous studies suggest that the nasopharyngeal microbiome affects disease development. We therefore studied the effect of the nasopharyngeal microbiome on viral load and mucosal cytokine responses, two important factors influencing the pathophysiology of RSV disease. To determine the relation between (i) the microbiome of the upper respiratory tract, (ii) viral load, and (iii) host mucosal inflammation during an RSV infection, nasopharyngeal microbiota profiles of RSV infected infants (< 6 months) with different levels of disease severity and age-matched healthy controls were determined by 16S rRNA marker gene sequencing. The viral load was measured using qPCR. Nasopharyngeal CCL5, CXCL10, MMP9, IL6, and CXCL8 levels were determined with ELISA. Results Viral load in nasopharyngeal aspirates of patients associates significantly to total nasopharyngeal microbiota composition. Healthy infants (n = 21) and RSV patients (n = 54) display very distinct microbial patterns, primarily characterized by a loss in commensals like Veillonella and overrepresentation of opportunistic organisms like Haemophilus and Achromobacter in RSV-infected individuals. Furthermore, nasopharyngeal microbiota profiles are significantly different based on CXCL8 levels. CXCL8 is a chemokine that was previously found to be indicative for disease severity and for which we find Haemophilus abundance as the strongest predictor for CXCL8 levels. Conclusions The nasopharyngeal microbiota in young infants with RSV infection is marked by an overrepresentation of the genus Haemophilus. We present that this bacterium is associated with viral load and mucosal CXCL8 responses, both which are involved in RSV disease pathogenesis.http://link.springer.com/article/10.1186/s40168-017-0395-yChemokineMicrobiomeMucosal inflammationRSVViral load
spellingShingle Thomas H. A. Ederveen
Gerben Ferwerda
Inge M. Ahout
Marloes Vissers
Ronald de Groot
Jos Boekhorst
Harro M. Timmerman
Martijn A. Huynen
Sacha A. F. T. van Hijum
Marien I. de Jonge
Haemophilus is overrepresented in the nasopharynx of infants hospitalized with RSV infection and associated with increased viral load and enhanced mucosal CXCL8 responses
Microbiome
Chemokine
Microbiome
Mucosal inflammation
RSV
Viral load
title Haemophilus is overrepresented in the nasopharynx of infants hospitalized with RSV infection and associated with increased viral load and enhanced mucosal CXCL8 responses
title_full Haemophilus is overrepresented in the nasopharynx of infants hospitalized with RSV infection and associated with increased viral load and enhanced mucosal CXCL8 responses
title_fullStr Haemophilus is overrepresented in the nasopharynx of infants hospitalized with RSV infection and associated with increased viral load and enhanced mucosal CXCL8 responses
title_full_unstemmed Haemophilus is overrepresented in the nasopharynx of infants hospitalized with RSV infection and associated with increased viral load and enhanced mucosal CXCL8 responses
title_short Haemophilus is overrepresented in the nasopharynx of infants hospitalized with RSV infection and associated with increased viral load and enhanced mucosal CXCL8 responses
title_sort haemophilus is overrepresented in the nasopharynx of infants hospitalized with rsv infection and associated with increased viral load and enhanced mucosal cxcl8 responses
topic Chemokine
Microbiome
Mucosal inflammation
RSV
Viral load
url http://link.springer.com/article/10.1186/s40168-017-0395-y
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