IFN-gamma treatment at early stages of influenza virus infection protects mice from death in a NK cell-dependent manner.
Influenza pandemics are imminent and represent a major world health concern. Since vaccinations are expected to be less efficient in the coming years due to newly emerging influenza virus strains, novel antiviral therapies are urgently needed. Here, we show that influenza-infected mice, capable of clearing the virus in the early stages of infection, failed to control inflammation and death. Sequential administration of Interferon-gamma (IFN-gamma) at early stage of the infection protected infected mice from death in a NK cell-dependent manner. IFN-gamma treatment stimulated NK cell proliferation and function and increased their number in the bone marrow, blood, spleen, and infected lungs, keeping viral clearance intact. In parallel, IFN-gamma treatment significantly reduced the number of T cells and NKT cells in the lungs at the inflammatory phase following infection. Thus, rapidly clearing the virus and reducing inflammation by shaping the cellular and cytokine profiles in the early stages of infection may favorably change the fate of influenza pathogenesis.
Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Jerusalem, Israel.
Ido D
ID
Weiss
Ori
O
Wald
Hanna
H
Wald
Katia
K
Beider
Michal
M
Abraham
Eithan
E
Galun
Arnon
A
Nagler
Amnon
A
Peled
D000818:Animals; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006386:Hemagglutination Tests; D016130:Immunophenotyping; D009980:Influenza A virus / Q000276:immunology* / Q000472:pathogenicity; D007371:Interferon-gamma / Q000008:administration & dosage*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008168:Lung / Q000473:pathology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000276:immunology*; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D019562:Viral Load / Q000187:drug effects
D007371:Interferon-gamma