Delivery of GM-CSF to Protect against Influenza Pneumonia.
BACKGROUND
Since adaptive immunity is thought to be central to immunity against influenza A virus (IAV) pneumonias, preventive strategies have focused primarily on vaccines. However, vaccine efficacy has been variable, in part because of antigenic shift and drift in circulating influenza viruses. Recent studies have highlighted the importance of innate immunity in protecting against influenza.


METHODS
Granulocyte-macrophage colony stimulating factor (GM-CSF) contributes to maturation of mononuclear phagocytes, enhancing their capacity for phagocytosis and cytokine production.


RESULTS
Overexpression of granulocyte macrophage-colony stimulating factor (GM-CSF) in the lung of transgenic mice provides remarkable protection against IAV, which depends on alveolar macrophages (AM). In this study, we report that pulmonary delivery of GM-CSF to wild type young and aged mice abrogated mortality from IAV.


CONCLUSIONS
We also demonstrate that protection is species specific and human GM-CSF do not protect the mice nor stimulates mouse immunity. We also show that IAV-induced lung injury is the culprit for side-effects of GM-CSF in treating mice after IAV infection, and introduce a novel strategy to deliver the GM-CSF to and retain it in the alveolar space even after IAV infection.
Center for Pulmonary and Infectious Diseases Control (CPIDC), The University of Texas Health Science Center at Tyler, 11937 U.S. Highway 271, Tyler, TX, United States of America.
Renuka
R
Subramaniam
Center for Pulmonary and Infectious Diseases Control (CPIDC), The University of Texas Health Science Center at Tyler, 11937 U.S. Highway 271, Tyler, TX, United States of America.
Zachary
Z
Hillberry
Center for Pulmonary and Infectious Diseases Control (CPIDC), The University of Texas Health Science Center at Tyler, 11937 U.S. Highway 271, Tyler, TX, United States of America.
Han
H
Chen
Center for Pulmonary and Infectious Diseases Control (CPIDC), The University of Texas Health Science Center at Tyler, 11937 U.S. Highway 271, Tyler, TX, United States of America.
Yan
Y
Feng
Center for Pulmonary and Infectious Diseases Control (CPIDC), The University of Texas Health Science Center at Tyler, 11937 U.S. Highway 271, Tyler, TX, United States of America.
Kalyn
K
Fletcher
Biomedical Research, The University of Texas Health Science Center at Tyler, U.S. Highway 271, Tyler, TX, USA.
Pierre
P
Neuenschwander
Center for Pulmonary and Infectious Diseases Control (CPIDC), The University of Texas Health Science Center at Tyler, 11937 U.S. Highway 271, Tyler, TX, United States of America.
Homayoun
H
Shams
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism / Q000821:virology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D010587:Phagocytosis / Q000187:drug effects; D011014:Pneumonia / Q000517:prevention & control*; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045663:Quantum Dots / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D014057:Tomography, X-Ray Computed
D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D020011:Protective Agents; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor