Inflammation induced by influenza virus impairs innate control of human pneumococcal carriage

Jochems, S. P.; Marcon, F.; Carniel, B. F.; Holloway, M.; Mitsi, E.; Smith, E.; Gritzfeld, J. F.; Solorzano, C.; Reine, J.; Pojar, S.; Nikolaou, E.; German, E. L.; Hyder-Wright, A.; Hill, H.; Hales, C.; de Steenhuijsen Piters, W. A. A.; Bogaert, D.; Adler, H.; Zaidi, S.; Connor, V.; Rylance, J.; Nakaya, H. I.; Ferreira, D. M.

doi:10.1101/347161

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bioRxiv · 10.1101/347161

Inflammation induced by influenza virus impairs innate control of human pneumococcal carriage

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Abstract

Secondary bacterial pneumonia following influenza infection is a significant cause of mortality worldwide. Upper respiratory tract pneumococcal carriage is important as both determinants of disease and population transmission. The immunological mechanisms that contain pneumococcal carriage are well-studied in mice but remain unclear in humans. Loss of this control of carriage following influenza infection is associated with secondary bacterial pneumonia during seasonal and pandemic outbreaks. We used a human type 6B pneumococcal challenge model to show that carriage acquisition induces early degranulation of resident neutrophils and recruitment of monocytes to the nose. Monocyte function associated with clearance of pneumococcal carriage. Prior nasal infection with live attenuated influenza virus induced inflammation, impaired innate function and altered genome-wide nasal gene responses to pneumococcal carriage. Levels of the cytokine IP-10 promoted by viral infection at the time of pneumococcal encounter was positively associated with bacterial density. These findings provide novel insights in nasal immunity to pneumococcus and viral-bacterial interactions during co-infection.

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Jochems, S. P., Marcon, F., Carniel, B. F., Holloway, M., Mitsi, E., Smith, E., Gritzfeld, J. F., Solorzano, C., Reine, J., Pojar, S., Nikolaou, E., German, E. L., Hyder-Wright, A., Hill, H., Hales, C., de Steenhuijsen Piters, W. A. A., Bogaert, D., Adler, H., Zaidi, S., Connor, V., Rylance, J., Nakaya, H. I., Ferreira, D. M.. 2018-06-20. Inflammation induced by influenza virus impairs innate control of human pneumococcal carriage. https://doi.org/10.1101/347161

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