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

Simon P Jochems; Fernando Marcon; Beatriz F Carniel; Mark Holloway; Elena Mitsi; Emma Smith; Jenna F Gritzfeld; Carla Solórzano; Jesús Reiné; 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 Connor; Stephen B Gordon; Jamie Rylance; Helder I Nakaya; Daniela M Ferreira

doi:10.1038/s41590-018-0231-y

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

Simon P Jochems, Fernando Marcon, Beatriz F Carniel, Mark Holloway, Elena Mitsi, Emma Smith, Jenna F Gritzfeld, Carla Solórzano, Jesús Reiné, 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 journal › Article › Academic › peer-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 language	English
Pages (from-to)	1299-1308
Number of pages	10
Journal	Nature immunology
Volume	19
Issue number	12
Early online date	2018
DOIs	https://doi.org/10.1038/s41590-018-0231-y
Publication status	Published - Dec 2018

Keywords

Journal Article
Immunity, Innate/immunology
Double-Blind Method
Humans
Nasal Mucosa/immunology
Influenza, Human/immunology
Inflammation/immunology
Streptococcus pneumoniae
Pneumococcal Infections/immunology
Neutrophils/immunology
Chemokine CXCL10/immunology
Monocytes/immunology
Coinfection/immunology
Chemotaxis, Leukocyte/immunology

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10.1038/s41590-018-0231-y

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Jochems, S. P., Marcon, F., Carniel, B. F., Holloway, M., Mitsi, E., Smith, E., Gritzfeld, J. F., Solórzano, C., Reiné, 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., ... Ferreira, D. M. (2018). Inflammation induced by influenza virus impairs human innate immune control of pneumococcus. Nature immunology, 19(12), 1299-1308. https://doi.org/10.1038/s41590-018-0231-y

@article{37f922ee5d7840109741b79d134ef3c4,

title = "Inflammation induced by influenza virus impairs human innate immune control of pneumococcus",

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.",

keywords = "Journal Article, Immunity, Innate/immunology, Double-Blind Method, Humans, Nasal Mucosa/immunology, Influenza, Human/immunology, Inflammation/immunology, Streptococcus pneumoniae, Pneumococcal Infections/immunology, Neutrophils/immunology, Chemokine CXCL10/immunology, Monocytes/immunology, Coinfection/immunology, Chemotaxis, Leukocyte/immunology",

author = "Jochems, {Simon P} and Fernando Marcon and Carniel, {Beatriz F} and Mark Holloway and Elena Mitsi and Emma Smith and Gritzfeld, {Jenna F} and Carla Sol{\'o}rzano and Jes{\'u}s Rein{\'e} and Sherin Pojar and Elissavet Nikolaou and German, {Esther L} and Angie Hyder-Wright and Helen Hill and Caz Hales and {de Steenhuijsen Piters}, {Wouter A A} and Debby Bogaert and Hugh Adler and Seher Zaidi and Victoria Connor and Gordon, {Stephen B} and Jamie Rylance and Nakaya, {Helder I} and Ferreira, {Daniela M}",

note = "Funding Information: S.B.G. and D.M.F. are supported by the Medical Research Council (grant MR/ M011569/1), the Bill and Melinda Gates Foundation (grant OPP1117728) and the National Institute for Health Research Local Comprehensive Research Network. Flow cytometric acquisition was performed on a BD LSR II funded by a Wellcome Trust Multi-User Equipment Grant (104936/Z/14/Z). S.P.J. received support from the Royal Society of Tropical Medicine and Hygiene for NanoString analysis. H.I.N. is supported by the S{\~a}o Paulo Research Foundation (FAPESP; grants 2013/08216-2 and 2012/19278-6). We thank all volunteers for participating in this study, and R. Robinson, C. Lowe, L. Lazarova, K. Piddock and I. Wheeler for clinical support. We also acknowledge M. Mina for his input in study design. Publisher Copyright: {\textcopyright} 2018, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2018",

month = dec,

doi = "10.1038/s41590-018-0231-y",

language = "English",

volume = "19",

pages = "1299--1308",

journal = "Nature immunology",

issn = "1529-2908",

publisher = "Nature Publishing Group",

number = "12",

}

Jochems, SP, Marcon, F, Carniel, BF, Holloway, M, Mitsi, E, Smith, E, Gritzfeld, JF, Solórzano, C, Reiné, J, Pojar, S, Nikolaou, E, German, EL, Hyder-Wright, A, Hill, H, Hales, C, de Steenhuijsen Piters, WAA, Bogaert, D, Adler, H, Zaidi, S, Connor, V, Gordon, SB, Rylance, J, Nakaya, HI & Ferreira, DM 2018, 'Inflammation induced by influenza virus impairs human innate immune control of pneumococcus', Nature immunology, vol. 19, no. 12, pp. 1299-1308. https://doi.org/10.1038/s41590-018-0231-y

TY - JOUR

T1 - Inflammation induced by influenza virus impairs human innate immune control of pneumococcus

AU - Jochems, Simon P

AU - Marcon, Fernando

AU - Carniel, Beatriz F

AU - Holloway, Mark

AU - Mitsi, Elena

AU - Smith, Emma

AU - Gritzfeld, Jenna F

AU - Solórzano, Carla

AU - Reiné, Jesús

AU - Pojar, Sherin

AU - Nikolaou, Elissavet

AU - German, Esther L

AU - Hyder-Wright, Angie

AU - Hill, Helen

AU - Hales, Caz

AU - de Steenhuijsen Piters, Wouter A A

AU - Bogaert, Debby

AU - Adler, Hugh

AU - Zaidi, Seher

AU - Connor, Victoria

AU - Gordon, Stephen B

AU - Rylance, Jamie

AU - Nakaya, Helder I

AU - Ferreira, Daniela M

N1 - Funding Information: S.B.G. and D.M.F. are supported by the Medical Research Council (grant MR/ M011569/1), the Bill and Melinda Gates Foundation (grant OPP1117728) and the National Institute for Health Research Local Comprehensive Research Network. Flow cytometric acquisition was performed on a BD LSR II funded by a Wellcome Trust Multi-User Equipment Grant (104936/Z/14/Z). S.P.J. received support from the Royal Society of Tropical Medicine and Hygiene for NanoString analysis. H.I.N. is supported by the São Paulo Research Foundation (FAPESP; grants 2013/08216-2 and 2012/19278-6). We thank all volunteers for participating in this study, and R. Robinson, C. Lowe, L. Lazarova, K. Piddock and I. Wheeler for clinical support. We also acknowledge M. Mina for his input in study design. Publisher Copyright: © 2018, The Author(s), under exclusive licence to Springer Nature America, Inc.

PY - 2018/12

Y1 - 2018/12

N2 - 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.

AB - 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.

KW - Journal Article

KW - Immunity, Innate/immunology

KW - Double-Blind Method

KW - Humans

KW - Nasal Mucosa/immunology

KW - Influenza, Human/immunology

KW - Inflammation/immunology

KW - Streptococcus pneumoniae

KW - Pneumococcal Infections/immunology

KW - Neutrophils/immunology

KW - Chemokine CXCL10/immunology

KW - Monocytes/immunology

KW - Coinfection/immunology

KW - Chemotaxis, Leukocyte/immunology

UR - http://www.scopus.com/inward/record.url?scp=85055963913&partnerID=8YFLogxK

U2 - 10.1038/s41590-018-0231-y

DO - 10.1038/s41590-018-0231-y

M3 - Article

C2 - 30374129

SN - 1529-2908

VL - 19

SP - 1299

EP - 1308

JO - Nature immunology

JF - Nature immunology

IS - 12

ER -

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

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