GM-CSF in the Lung Protects Against Lethal Influenza Infection

Overview

Journal Am J Respir Crit Care Med

Specialty Critical Care

Date 2011 Apr 9

PMID 21474645

Citations 96

Authors

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

Affiliations

Soon will be listed here.

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/macrophage colony-stimulating factor (GM-CSF) in the lung increases resistance to influenza.

Methods: Wild-type mice and transgenic mice 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 Main Results: Wild-type mice 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 showed histologic 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.

Citing Articles

Alveolar Macrophages in Viral Respiratory Infections: Sentinels and Saboteurs of Lung Defense.

Popperl P, Stoff M, Beineke A Int J Mol Sci. 2025; 26(1.

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Inhaled GM-CSF administered during ongoing pneumovirus infection alters myeloid and CD8 T cell immunity without affecting disease outcome.

Debeuf N, Deckers J, Lameire S, Bosteels C, Hammad H, Lambrecht B Front Immunol. 2024; 15:1439789.

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Lung Immune Cell Niches and the Discovery of New Cell Subtypes.

Shan Q, Qiu J, Dong Z, Xu X, Zhang S, Ma J Adv Sci (Weinh). 2024; 11(45):e2405490.

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IFN-γ primes bone marrow neutrophils to acquire regulatory functions in severe viral respiratory infections.

Creusat F, Jouan Y, Gonzalez L, Barsac E, Ilango G, Lemoine R Sci Adv. 2024; 10(41):eadn3257.

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The role of alveolar macrophages in viral respiratory infections and their therapeutic implications.

Javaherdehi A, Ghanbari S, Mahdavi P, Zafarani A, Razizadeh M Biochem Biophys Rep. 2024; 40:101826.

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