Nasopharyngeal microbiota, host transcriptome, and disease severity in children with respiratory syncytial virus infection

Wouter A A De Steenhuijsen Piters, Santtu Heinonen, Raiza Hasrat, Eleonora Bunsow, Bennett Smith, Maria Carmen Suarez-Arrabal, Damien J. Chaussabel, Daniel M. Cohen, Elisabeth A M Sanders, Octavio Ramilo, Debby Bogaert, Asuncion Mejias

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Rationale: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variabilityofRSVdiseaseseverity,especiallyamonghealthychildren.We postulate that the severity of RSV infection is influenced by modulation of the host immune response by the local bacterial ecosystem. Objectives: To assess whether specific nasopharyngeal microbiota (clusters) are associated with distinct host transcriptome profiles and diseaseseverityinchildrenlessthan2years ofagewithRSVinfection. Methods: We characterized the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy children by 16S-rRNA sequencing. In parallel, using multivariable models, we analyzed whole-blood transcriptome profiles to study the relationship between microbial community composition, the RSVinduced host transcriptional response, and clinical disease severity. Measurements and Main Results: We identified five nasopharyngeal microbiota clusters characterized by enrichment of either Haemophilus influenzae, Streptococcus, Corynebacterium, Moraxella, or Staphylococcus aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus and negatively associated with S. aureus abundance, independent of age. Children with RSV showed overexpression of IFN-related genes, independent of the microbiota cluster. In addition, transcriptome profiles of children with RSV infection and H. influenzae-and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to Toll-like receptor and by neutrophil and macrophage activation and signaling. Conclusions: Our data suggest that interactions between RSV and nasopharyngeal microbiota might modulate the host immune response, potentially affecting clinical disease severity.

Original languageEnglish
Pages (from-to)1104-1115
Number of pages12
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume194
Issue number9
DOIs
Publication statusPublished - 1 Nov 2016
Externally publishedYes

Fingerprint

Respiratory Syncytial Virus Infections
Microbiota
Transcriptome
Respiratory Syncytial Viruses
Haemophilus influenzae
Streptococcus
Staphylococcus aureus
Hospitalization
Moraxella
Corynebacterium
Neutrophil Activation
Macrophage Activation
Toll-Like Receptors
Virus Diseases
Respiratory Tract Infections
Genes
Ecosystem

Keywords

  • Disease severity
  • Microbiota
  • Nasopharynx
  • Respiratory syncytial virus
  • Transcriptome profiling

ASJC Scopus subject areas

  • Medicine(all)
  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

De Steenhuijsen Piters, W. A. A., Heinonen, S., Hasrat, R., Bunsow, E., Smith, B., Suarez-Arrabal, M. C., ... Mejias, A. (2016). Nasopharyngeal microbiota, host transcriptome, and disease severity in children with respiratory syncytial virus infection. American Journal of Respiratory and Critical Care Medicine, 194(9), 1104-1115. https://doi.org/10.1164/rccm.201602-0220OC

Nasopharyngeal microbiota, host transcriptome, and disease severity in children with respiratory syncytial virus infection. / De Steenhuijsen Piters, Wouter A A; Heinonen, Santtu; Hasrat, Raiza; Bunsow, Eleonora; Smith, Bennett; Suarez-Arrabal, Maria Carmen; Chaussabel, Damien J.; Cohen, Daniel M.; Sanders, Elisabeth A M; Ramilo, Octavio; Bogaert, Debby; Mejias, Asuncion.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 194, No. 9, 01.11.2016, p. 1104-1115.

Research output: Contribution to journalArticle

De Steenhuijsen Piters, WAA, Heinonen, S, Hasrat, R, Bunsow, E, Smith, B, Suarez-Arrabal, MC, Chaussabel, DJ, Cohen, DM, Sanders, EAM, Ramilo, O, Bogaert, D & Mejias, A 2016, 'Nasopharyngeal microbiota, host transcriptome, and disease severity in children with respiratory syncytial virus infection', American Journal of Respiratory and Critical Care Medicine, vol. 194, no. 9, pp. 1104-1115. https://doi.org/10.1164/rccm.201602-0220OC
De Steenhuijsen Piters, Wouter A A ; Heinonen, Santtu ; Hasrat, Raiza ; Bunsow, Eleonora ; Smith, Bennett ; Suarez-Arrabal, Maria Carmen ; Chaussabel, Damien J. ; Cohen, Daniel M. ; Sanders, Elisabeth A M ; Ramilo, Octavio ; Bogaert, Debby ; Mejias, Asuncion. / Nasopharyngeal microbiota, host transcriptome, and disease severity in children with respiratory syncytial virus infection. In: American Journal of Respiratory and Critical Care Medicine. 2016 ; Vol. 194, No. 9. pp. 1104-1115.
@article{b68814e4bca340a1a8c02e11f21bf340,
title = "Nasopharyngeal microbiota, host transcriptome, and disease severity in children with respiratory syncytial virus infection",
abstract = "Rationale: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variabilityofRSVdiseaseseverity,especiallyamonghealthychildren.We postulate that the severity of RSV infection is influenced by modulation of the host immune response by the local bacterial ecosystem. Objectives: To assess whether specific nasopharyngeal microbiota (clusters) are associated with distinct host transcriptome profiles and diseaseseverityinchildrenlessthan2years ofagewithRSVinfection. Methods: We characterized the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy children by 16S-rRNA sequencing. In parallel, using multivariable models, we analyzed whole-blood transcriptome profiles to study the relationship between microbial community composition, the RSVinduced host transcriptional response, and clinical disease severity. Measurements and Main Results: We identified five nasopharyngeal microbiota clusters characterized by enrichment of either Haemophilus influenzae, Streptococcus, Corynebacterium, Moraxella, or Staphylococcus aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus and negatively associated with S. aureus abundance, independent of age. Children with RSV showed overexpression of IFN-related genes, independent of the microbiota cluster. In addition, transcriptome profiles of children with RSV infection and H. influenzae-and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to Toll-like receptor and by neutrophil and macrophage activation and signaling. Conclusions: Our data suggest that interactions between RSV and nasopharyngeal microbiota might modulate the host immune response, potentially affecting clinical disease severity.",
keywords = "Disease severity, Microbiota, Nasopharynx, Respiratory syncytial virus, Transcriptome profiling",
author = "{De Steenhuijsen Piters}, {Wouter A A} and Santtu Heinonen and Raiza Hasrat and Eleonora Bunsow and Bennett Smith and Suarez-Arrabal, {Maria Carmen} and Chaussabel, {Damien J.} and Cohen, {Daniel M.} and Sanders, {Elisabeth A M} and Octavio Ramilo and Debby Bogaert and Asuncion Mejias",
year = "2016",
month = "11",
day = "1",
doi = "10.1164/rccm.201602-0220OC",
language = "English",
volume = "194",
pages = "1104--1115",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "9",

}

TY - JOUR

T1 - Nasopharyngeal microbiota, host transcriptome, and disease severity in children with respiratory syncytial virus infection

AU - De Steenhuijsen Piters, Wouter A A

AU - Heinonen, Santtu

AU - Hasrat, Raiza

AU - Bunsow, Eleonora

AU - Smith, Bennett

AU - Suarez-Arrabal, Maria Carmen

AU - Chaussabel, Damien J.

AU - Cohen, Daniel M.

AU - Sanders, Elisabeth A M

AU - Ramilo, Octavio

AU - Bogaert, Debby

AU - Mejias, Asuncion

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Rationale: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variabilityofRSVdiseaseseverity,especiallyamonghealthychildren.We postulate that the severity of RSV infection is influenced by modulation of the host immune response by the local bacterial ecosystem. Objectives: To assess whether specific nasopharyngeal microbiota (clusters) are associated with distinct host transcriptome profiles and diseaseseverityinchildrenlessthan2years ofagewithRSVinfection. Methods: We characterized the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy children by 16S-rRNA sequencing. In parallel, using multivariable models, we analyzed whole-blood transcriptome profiles to study the relationship between microbial community composition, the RSVinduced host transcriptional response, and clinical disease severity. Measurements and Main Results: We identified five nasopharyngeal microbiota clusters characterized by enrichment of either Haemophilus influenzae, Streptococcus, Corynebacterium, Moraxella, or Staphylococcus aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus and negatively associated with S. aureus abundance, independent of age. Children with RSV showed overexpression of IFN-related genes, independent of the microbiota cluster. In addition, transcriptome profiles of children with RSV infection and H. influenzae-and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to Toll-like receptor and by neutrophil and macrophage activation and signaling. Conclusions: Our data suggest that interactions between RSV and nasopharyngeal microbiota might modulate the host immune response, potentially affecting clinical disease severity.

AB - Rationale: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variabilityofRSVdiseaseseverity,especiallyamonghealthychildren.We postulate that the severity of RSV infection is influenced by modulation of the host immune response by the local bacterial ecosystem. Objectives: To assess whether specific nasopharyngeal microbiota (clusters) are associated with distinct host transcriptome profiles and diseaseseverityinchildrenlessthan2years ofagewithRSVinfection. Methods: We characterized the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy children by 16S-rRNA sequencing. In parallel, using multivariable models, we analyzed whole-blood transcriptome profiles to study the relationship between microbial community composition, the RSVinduced host transcriptional response, and clinical disease severity. Measurements and Main Results: We identified five nasopharyngeal microbiota clusters characterized by enrichment of either Haemophilus influenzae, Streptococcus, Corynebacterium, Moraxella, or Staphylococcus aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus and negatively associated with S. aureus abundance, independent of age. Children with RSV showed overexpression of IFN-related genes, independent of the microbiota cluster. In addition, transcriptome profiles of children with RSV infection and H. influenzae-and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to Toll-like receptor and by neutrophil and macrophage activation and signaling. Conclusions: Our data suggest that interactions between RSV and nasopharyngeal microbiota might modulate the host immune response, potentially affecting clinical disease severity.

KW - Disease severity

KW - Microbiota

KW - Nasopharynx

KW - Respiratory syncytial virus

KW - Transcriptome profiling

UR - http://www.scopus.com/inward/record.url?scp=84994812757&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84994812757&partnerID=8YFLogxK

U2 - 10.1164/rccm.201602-0220OC

DO - 10.1164/rccm.201602-0220OC

M3 - Article

VL - 194

SP - 1104

EP - 1115

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 9

ER -