Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections

Hazem E. Ghoneim, Paul G. Thomas, Jonathan Mccullers

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Viruses such as influenza suppress host immune function by a variety of methods. This may result in significant morbidity through several pathways, including facilitation of secondary bacterial pneumonia from pathogens such as Streptococcus pneumoniae. PKH26-phagocytic cell labeling dye was administered intranasally to label resident alveolar macrophages (AMs) in a wellestablished murine model before influenza infection to determine turnover kinetics during the course of infection. More than 90% of resident AMs were lost in the first week after influenza, whereas the remaining cells had a necrotic phenotype. To establish the impact of this innate immune defect, influenza-infected mice were challenged with S. pneumoniae. Early AM-mediated bacterial clearance was significantly impaired in influenza-infected mice: ~50% of the initial bacterial inoculum could be harvested from the alveolar airspace 3 h later. In mock-infected mice, by contrast, >95% of inocula up to 50-fold higher was efficiently cleared. Coinfection during the AM depletion phase caused significant body weight loss and mortality. Two weeks after influenza, the AM population was fully replenished with successful re-establishment of early innate host protection. Local GMCSF treatment partially restored the impaired early bacterial clearance with efficient protection against secondary pneumococcal pneumonia. We conclude that resident AM depletion occurs during influenza infection. Among other potential effects, this establishes a niche for secondary pneumococcal infection by altering early cellular innate immunity in the lungs, resulting in pneumococcal outgrowth and lethal pneumonia. This novel mechanism will inform development of novel therapeutic approaches to restore lung innate immunity against bacterial superinfections.

Original languageEnglish (US)
Pages (from-to)1250-1259
Number of pages10
JournalJournal of Immunology
Volume191
Issue number3
DOIs
StatePublished - Aug 1 2013

Fingerprint

Superinfection
Alveolar Macrophages
Bacterial Infections
Human Influenza
Streptococcus pneumoniae
Coinfection
Innate Immunity
Infection
Pneumococcal Pneumonia
Pneumococcal Infections
Bacterial Pneumonia
Lung
Phagocytes
Cellular Immunity
Weight Loss
Pneumonia
Coloring Agents
Body Weight
Viruses
Morbidity

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections. / Ghoneim, Hazem E.; Thomas, Paul G.; Mccullers, Jonathan.

In: Journal of Immunology, Vol. 191, No. 3, 01.08.2013, p. 1250-1259.

Research output: Contribution to journalArticle

@article{6a56664154954418ad7f46d59606daab,
title = "Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections",
abstract = "Viruses such as influenza suppress host immune function by a variety of methods. This may result in significant morbidity through several pathways, including facilitation of secondary bacterial pneumonia from pathogens such as Streptococcus pneumoniae. PKH26-phagocytic cell labeling dye was administered intranasally to label resident alveolar macrophages (AMs) in a wellestablished murine model before influenza infection to determine turnover kinetics during the course of infection. More than 90{\%} of resident AMs were lost in the first week after influenza, whereas the remaining cells had a necrotic phenotype. To establish the impact of this innate immune defect, influenza-infected mice were challenged with S. pneumoniae. Early AM-mediated bacterial clearance was significantly impaired in influenza-infected mice: ~50{\%} of the initial bacterial inoculum could be harvested from the alveolar airspace 3 h later. In mock-infected mice, by contrast, >95{\%} of inocula up to 50-fold higher was efficiently cleared. Coinfection during the AM depletion phase caused significant body weight loss and mortality. Two weeks after influenza, the AM population was fully replenished with successful re-establishment of early innate host protection. Local GMCSF treatment partially restored the impaired early bacterial clearance with efficient protection against secondary pneumococcal pneumonia. We conclude that resident AM depletion occurs during influenza infection. Among other potential effects, this establishes a niche for secondary pneumococcal infection by altering early cellular innate immunity in the lungs, resulting in pneumococcal outgrowth and lethal pneumonia. This novel mechanism will inform development of novel therapeutic approaches to restore lung innate immunity against bacterial superinfections.",
author = "Ghoneim, {Hazem E.} and Thomas, {Paul G.} and Jonathan Mccullers",
year = "2013",
month = "8",
day = "1",
doi = "10.4049/jimmunol.1300014",
language = "English (US)",
volume = "191",
pages = "1250--1259",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections

AU - Ghoneim, Hazem E.

AU - Thomas, Paul G.

AU - Mccullers, Jonathan

PY - 2013/8/1

Y1 - 2013/8/1

N2 - Viruses such as influenza suppress host immune function by a variety of methods. This may result in significant morbidity through several pathways, including facilitation of secondary bacterial pneumonia from pathogens such as Streptococcus pneumoniae. PKH26-phagocytic cell labeling dye was administered intranasally to label resident alveolar macrophages (AMs) in a wellestablished murine model before influenza infection to determine turnover kinetics during the course of infection. More than 90% of resident AMs were lost in the first week after influenza, whereas the remaining cells had a necrotic phenotype. To establish the impact of this innate immune defect, influenza-infected mice were challenged with S. pneumoniae. Early AM-mediated bacterial clearance was significantly impaired in influenza-infected mice: ~50% of the initial bacterial inoculum could be harvested from the alveolar airspace 3 h later. In mock-infected mice, by contrast, >95% of inocula up to 50-fold higher was efficiently cleared. Coinfection during the AM depletion phase caused significant body weight loss and mortality. Two weeks after influenza, the AM population was fully replenished with successful re-establishment of early innate host protection. Local GMCSF treatment partially restored the impaired early bacterial clearance with efficient protection against secondary pneumococcal pneumonia. We conclude that resident AM depletion occurs during influenza infection. Among other potential effects, this establishes a niche for secondary pneumococcal infection by altering early cellular innate immunity in the lungs, resulting in pneumococcal outgrowth and lethal pneumonia. This novel mechanism will inform development of novel therapeutic approaches to restore lung innate immunity against bacterial superinfections.

AB - Viruses such as influenza suppress host immune function by a variety of methods. This may result in significant morbidity through several pathways, including facilitation of secondary bacterial pneumonia from pathogens such as Streptococcus pneumoniae. PKH26-phagocytic cell labeling dye was administered intranasally to label resident alveolar macrophages (AMs) in a wellestablished murine model before influenza infection to determine turnover kinetics during the course of infection. More than 90% of resident AMs were lost in the first week after influenza, whereas the remaining cells had a necrotic phenotype. To establish the impact of this innate immune defect, influenza-infected mice were challenged with S. pneumoniae. Early AM-mediated bacterial clearance was significantly impaired in influenza-infected mice: ~50% of the initial bacterial inoculum could be harvested from the alveolar airspace 3 h later. In mock-infected mice, by contrast, >95% of inocula up to 50-fold higher was efficiently cleared. Coinfection during the AM depletion phase caused significant body weight loss and mortality. Two weeks after influenza, the AM population was fully replenished with successful re-establishment of early innate host protection. Local GMCSF treatment partially restored the impaired early bacterial clearance with efficient protection against secondary pneumococcal pneumonia. We conclude that resident AM depletion occurs during influenza infection. Among other potential effects, this establishes a niche for secondary pneumococcal infection by altering early cellular innate immunity in the lungs, resulting in pneumococcal outgrowth and lethal pneumonia. This novel mechanism will inform development of novel therapeutic approaches to restore lung innate immunity against bacterial superinfections.

UR - http://www.scopus.com/inward/record.url?scp=84880666005&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880666005&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1300014

DO - 10.4049/jimmunol.1300014

M3 - Article

VL - 191

SP - 1250

EP - 1259

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -