GM-CSF in the Lung Protects against Lethal Influenza Infection

Fang Fang Huang, Peter F. Barnes, Yan Feng, Ruben Donis, Zissis C. Chroneos, Steven Idell, Timothy Allen, Daniel R. Perez, Jeffrey A. Whitsett, Kyri Dunussi-Joannopoulos, Homayoun Shams

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Rationale: Alveolar macrophages contribute to host defenses against influenza in animal models. Enhancing alveolar macrophage function may contribute to protection against influenza. Objectives: To determine if increased expression of granulocyte/ macrophagecolony-stimulatingfactor(GM-CSF) in the lungincreases resistance to influenza. Methods: Wild-typemice and transgenicmice that expressed GM-CSF in the lung were infected with influenza virus, and lung pathology, weight loss, and mortality were measured. We also administered GM-CSF to the lungs of wild-type mice that were infected with influenza virus. Measurements and MainResults: Wild-typemice all died after infection with different strains of influenza virus, but all transgenic mice expressing GM-CSF in the lungs survived. The latter also had greatly reduced weight loss and lung injury, and showedhistologic evidence of a rapid host inflammatory response that controlled infection. The resistance of transgenic mice to influenza was abrogated by elimination of alveolar phagocytes, but not by depletion of T cells, B cells, or neutrophils. Transgenic mice had far more alveolar macrophages than did wild-type mice, and they were more resistant to influenza-induced apoptosis. Delivery of intranasal GM-CSF to wild-type mice also conferred resistance to influenza. Conclusions: GM-CSF confers resistance to influenza by enhancing innate immune mechanisms that depend on alveolar macrophages. Pulmonary delivery of this cytokine has the potential to reduce the morbidity and mortality due to influenza virus.

Original languageEnglish (US)
Pages (from-to)259-268
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume184
Issue number2
DOIs
StatePublished - Jul 15 2011
Externally publishedYes

Fingerprint

Granulocytes
Human Influenza
Alveolar Macrophages
Lung
Orthomyxoviridae
Infection
Transgenic Mice
Weight Loss
Mortality
Lung Injury
Phagocytes
Neutrophils
B-Lymphocytes
Animal Models
Apoptosis
Pathology
Cytokines
Morbidity
T-Lymphocytes

Keywords

  • Alveolar macrophages
  • GM-CSF
  • Influenza

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Huang, F. F., Barnes, P. F., Feng, Y., Donis, R., Chroneos, Z. C., Idell, S., ... Shams, H. (2011). GM-CSF in the Lung Protects against Lethal Influenza Infection. American Journal of Respiratory and Critical Care Medicine, 184(2), 259-268. https://doi.org/10.1164/rccm.201012-2036OC

GM-CSF in the Lung Protects against Lethal Influenza Infection. / Huang, Fang Fang; Barnes, Peter F.; Feng, Yan; Donis, Ruben; Chroneos, Zissis C.; Idell, Steven; Allen, Timothy; Perez, Daniel R.; Whitsett, Jeffrey A.; Dunussi-Joannopoulos, Kyri; Shams, Homayoun.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 184, No. 2, 15.07.2011, p. 259-268.

Research output: Contribution to journalArticle

Huang, FF, Barnes, PF, Feng, Y, Donis, R, Chroneos, ZC, Idell, S, Allen, T, Perez, DR, Whitsett, JA, Dunussi-Joannopoulos, K & Shams, H 2011, 'GM-CSF in the Lung Protects against Lethal Influenza Infection', American Journal of Respiratory and Critical Care Medicine, vol. 184, no. 2, pp. 259-268. https://doi.org/10.1164/rccm.201012-2036OC
Huang, Fang Fang ; Barnes, Peter F. ; Feng, Yan ; Donis, Ruben ; Chroneos, Zissis C. ; Idell, Steven ; Allen, Timothy ; Perez, Daniel R. ; Whitsett, Jeffrey A. ; Dunussi-Joannopoulos, Kyri ; Shams, Homayoun. / GM-CSF in the Lung Protects against Lethal Influenza Infection. In: American Journal of Respiratory and Critical Care Medicine. 2011 ; Vol. 184, No. 2. pp. 259-268.
@article{207209075009442c83dd9cc6b4e39a30,
title = "GM-CSF in the Lung Protects against Lethal Influenza Infection",
abstract = "Rationale: Alveolar macrophages contribute to host defenses against influenza in animal models. Enhancing alveolar macrophage function may contribute to protection against influenza. Objectives: To determine if increased expression of granulocyte/ macrophagecolony-stimulatingfactor(GM-CSF) in the lungincreases resistance to influenza. Methods: Wild-typemice and transgenicmice that expressed GM-CSF in the lung were infected with influenza virus, and lung pathology, weight loss, and mortality were measured. We also administered GM-CSF to the lungs of wild-type mice that were infected with influenza virus. Measurements and MainResults: Wild-typemice all died after infection with different strains of influenza virus, but all transgenic mice expressing GM-CSF in the lungs survived. The latter also had greatly reduced weight loss and lung injury, and showedhistologic evidence of a rapid host inflammatory response that controlled infection. The resistance of transgenic mice to influenza was abrogated by elimination of alveolar phagocytes, but not by depletion of T cells, B cells, or neutrophils. Transgenic mice had far more alveolar macrophages than did wild-type mice, and they were more resistant to influenza-induced apoptosis. Delivery of intranasal GM-CSF to wild-type mice also conferred resistance to influenza. Conclusions: GM-CSF confers resistance to influenza by enhancing innate immune mechanisms that depend on alveolar macrophages. Pulmonary delivery of this cytokine has the potential to reduce the morbidity and mortality due to influenza virus.",
keywords = "Alveolar macrophages, GM-CSF, Influenza",
author = "Huang, {Fang Fang} and Barnes, {Peter F.} and Yan Feng and Ruben Donis and Chroneos, {Zissis C.} and Steven Idell and Timothy Allen and Perez, {Daniel R.} and Whitsett, {Jeffrey A.} and Kyri Dunussi-Joannopoulos and Homayoun Shams",
year = "2011",
month = "7",
day = "15",
doi = "10.1164/rccm.201012-2036OC",
language = "English (US)",
volume = "184",
pages = "259--268",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "2",

}

TY - JOUR

T1 - GM-CSF in the Lung Protects against Lethal Influenza Infection

AU - Huang, Fang Fang

AU - Barnes, Peter F.

AU - Feng, Yan

AU - Donis, Ruben

AU - Chroneos, Zissis C.

AU - Idell, Steven

AU - Allen, Timothy

AU - Perez, Daniel R.

AU - Whitsett, Jeffrey A.

AU - Dunussi-Joannopoulos, Kyri

AU - Shams, Homayoun

PY - 2011/7/15

Y1 - 2011/7/15

N2 - Rationale: Alveolar macrophages contribute to host defenses against influenza in animal models. Enhancing alveolar macrophage function may contribute to protection against influenza. Objectives: To determine if increased expression of granulocyte/ macrophagecolony-stimulatingfactor(GM-CSF) in the lungincreases resistance to influenza. Methods: Wild-typemice and transgenicmice that expressed GM-CSF in the lung were infected with influenza virus, and lung pathology, weight loss, and mortality were measured. We also administered GM-CSF to the lungs of wild-type mice that were infected with influenza virus. Measurements and MainResults: Wild-typemice all died after infection with different strains of influenza virus, but all transgenic mice expressing GM-CSF in the lungs survived. The latter also had greatly reduced weight loss and lung injury, and showedhistologic evidence of a rapid host inflammatory response that controlled infection. The resistance of transgenic mice to influenza was abrogated by elimination of alveolar phagocytes, but not by depletion of T cells, B cells, or neutrophils. Transgenic mice had far more alveolar macrophages than did wild-type mice, and they were more resistant to influenza-induced apoptosis. Delivery of intranasal GM-CSF to wild-type mice also conferred resistance to influenza. Conclusions: GM-CSF confers resistance to influenza by enhancing innate immune mechanisms that depend on alveolar macrophages. Pulmonary delivery of this cytokine has the potential to reduce the morbidity and mortality due to influenza virus.

AB - Rationale: Alveolar macrophages contribute to host defenses against influenza in animal models. Enhancing alveolar macrophage function may contribute to protection against influenza. Objectives: To determine if increased expression of granulocyte/ macrophagecolony-stimulatingfactor(GM-CSF) in the lungincreases resistance to influenza. Methods: Wild-typemice and transgenicmice that expressed GM-CSF in the lung were infected with influenza virus, and lung pathology, weight loss, and mortality were measured. We also administered GM-CSF to the lungs of wild-type mice that were infected with influenza virus. Measurements and MainResults: Wild-typemice all died after infection with different strains of influenza virus, but all transgenic mice expressing GM-CSF in the lungs survived. The latter also had greatly reduced weight loss and lung injury, and showedhistologic evidence of a rapid host inflammatory response that controlled infection. The resistance of transgenic mice to influenza was abrogated by elimination of alveolar phagocytes, but not by depletion of T cells, B cells, or neutrophils. Transgenic mice had far more alveolar macrophages than did wild-type mice, and they were more resistant to influenza-induced apoptosis. Delivery of intranasal GM-CSF to wild-type mice also conferred resistance to influenza. Conclusions: GM-CSF confers resistance to influenza by enhancing innate immune mechanisms that depend on alveolar macrophages. Pulmonary delivery of this cytokine has the potential to reduce the morbidity and mortality due to influenza virus.

KW - Alveolar macrophages

KW - GM-CSF

KW - Influenza

UR - http://www.scopus.com/inward/record.url?scp=80051553380&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051553380&partnerID=8YFLogxK

U2 - 10.1164/rccm.201012-2036OC

DO - 10.1164/rccm.201012-2036OC

M3 - Article

VL - 184

SP - 259

EP - 268

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 2

ER -