Airway response to respiratory syncytial virus has incidental antibacterial effects

Abstract

RSV infection is typically associated with secondary bacterial infection. We hypothesise that the local airway immune response to RSV has incidental antibacterial effects. Using coordinated proteomics and metagenomics analysis we simultaneously analysed the microbiota and proteomes of the upper airway and determined direct antibacterial activity in airway secretions of RSV-infected children. Here, we report that the airway abundance of Streptococcus was higher in samples collected at the time of RSV infection compared with samples collected one month later. RSV infection is associated with neutrophil influx into the airway and degranulation and is marked by overexpression of proteins with known antibacterial activity including BPI, EPX, MPO and AZU1. Airway secretions of children infected with RSV, have significantly greater antibacterial activity compared to RSV-negative controls. This RSV-associated, neutrophil-mediated antibacterial response in the airway appears to act as a regulatory mechanism that modulates bacterial growth in the airways of RSV-infected children.

Identifying novel biomarkers of the pediatric influenza infection by weighted co-expression network analysis

“…The genes involved in the mediumpurple4 were enriched in the immune pathways and neutrophil degranulation. Neutrophils are granulocytes that comprise innate phagocytic cells packed with granules containing proteins with antibacterial function [42,43]. In this study, we identified proteins belonging to three types of neutrophil granules: primary (azurophilic: ELANE, MPO, PRTN3, BPI), secondary (specific: LTF, DEFA4, DEFA1, DEFA1B), and tertiary (gelatinase: PGLYRP1) granules.…”

Increased Moraxella and Streptococcus species abundance after severe bronchiolitis is associated with recurrent wheezing

“…Fifth, the present results are unable to untangle how host environmental conditions, including bacterial-bacterial interactions at the time of infection, might enhance the survival of certain species. 34 However, our group is currently examining the role of airway microbe-host relations in the development of childhood asthma.…”

A Meta-Analysis of Multiple Whole Blood Gene Expression Data Unveils a Diagnostic Host-Response Transcript Signature for Respiratory Syncytial Virus

“…Moreover, the study of the host gene expression response to RSV infection is usually restricted to specific and very homogeneous cohorts, hampering the interpretation of the results, the impact of the conclusions obtained and their translation into a molecular test that could be used in routine clinical practice. The present meta-analysis shows that RSV infection leads to global changes in the host transcriptome, affecting not only the transcriptomic machinery of the airway infected cells [28], but also the expression of hundreds of genes in blood cells (Table S2). In particular, according to our results, RSV alters the expression of >1,500 genes in the host compared to healthy controls, involving e.g., cell cycle and immune system genes.…”

“…It has been shown that neutrophils degranulate into the airway in response to RSV, pointing to a local innate response to the infection. Neutrophils degranulation implies the release of antimicrobial substances that may contribute to the control of commensal bacteria in the upper respiratory tract [28].…”