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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)1299–1308
Number of pages10
JournalNature Immunology
Volume19
Early online date29 Oct 2018
DOIs
Publication statusPublished - Dec 2018

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