Journal Article

Inflammation induced by influenza virus impairs human innate immune control of pneumococcus

Adler, Hugh, Hill, Helen, Nakaya, Helder I., Hales, Caz, Reiné, Jesús, Mitsi, Elena, Zaidi, Seher, Pojar, Sherin, Nikolaou, Elissavet, Connor, Victoria, Gordon, Stephen B., Holloway, Mark, Hyder-Wright, Angie, de Steenhuijsen Piters, Wouter A. A., Bogaert, Debby, Carniel, Beatriz F., Smith, Emma, German, Esther L., Rylance, Jamie, Jochems, Simon P., Ferreira, Daniela M., Marcon, Fernando, Gritzfeld, Jenna F., Solórzano, Carla

2018

Overview

Colonization of the upper respiratory tract by pneumococcus is important both as a determinant of disease and for transmission into the population. The immunological mechanisms that contain pneumococcus during colonization are well studied in mice but remain unclear in humans. Loss of this control of pneumococcus following infection with influenza virus is associated with secondary bacterial pneumonia. We used a human challenge model with type 6B pneumococcus to show that acquisition of pneumococcus induced early degranulation of resident neutrophils and recruitment of monocytes to the nose. Monocyte function was associated with the clearance of pneumococcus. Prior nasal infection with live attenuated influenza virus induced inflammation, impaired innate immune function and altered genome-wide nasal gene responses to the carriage of pneumococcus. Levels of the cytokine CXCL10, promoted by viral infection, at the time pneumococcus was encountered were positively associated with bacterial load. Pneumococcal carriage in the upper respiratory tract is an important determinant of influenza severity. Jochems et al. use human systems analysis to show that influenza-induced inflammation increases bacterial burden in the nasal cavity with implications for secondary bacterial pneumonia.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/250/255 / 631/250/262 / 692/420/256/2516 / 692/699/255 / Biomedical and Life Sciences / Biomedicine / Chemokine CXCL10 - immunology / Chemotaxis, Leukocyte - immunology / Coinfection - immunology / Colonization / CXCL10 protein / Degranulation / Disease susceptibility / Disease transmission / Double-Blind Method / Genes / Genetic aspects / Genomes / Genomics / Humans / Immune clearance / Immune response / Immune system / Immunity, Innate - immunology / Immunology / Infection / Infections / Infectious Diseases / Inflammation / Inflammation - immunology / Influenza / Influenza viruses / Influenza, Human - immunology / Leukocytes (neutrophilic) / Monocytes / Monocytes - immunology / Nasal Mucosa - immunology / Neutrophils - immunology / Nose / Physiological aspects / Pneumococcal Infections - immunology / Pneumonia / Population studies / Respiratory tract / Respiratory tract diseases / Risk factors / Sinusitis / Streptococcus infections / Streptococcus pneumoniae / Systems analysis / Viral infections / Virus diseases / Viruses