Open AccessInterleukin-15 Is Critical in the Pathogenesis of Influenza A Virus-Induced Acute Lung Injury
Author(s) -
Ryô Nakamura,
Naoyuki Maeda,
Kensuke Shibata,
Hisakata Yamada,
Tetsuo Kase,
Yasunobu Yoshikai
Publication year - 2010
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.02030-09
Subject(s) - biology , pathogenesis , virus , cytokine storm , adoptive cell transfer , influenza a virus , immunology , virology , cd8 , pneumonia , orthomyxoviridae , cytokine , monoclonal antibody , antigen , antibody , immune system , t cell , medicine , pathology , disease , covid-19 , infectious disease (medical specialty)
Highly pathogenic influenza A viruses cause acute severe pneumonia to which the occurrence of “cytokine storm” has been proposed to contribute. Here we show that interleukin-15 (IL-15) knockout (KO) mice exhibited reduced mortality after infection with influenza virus A/FM/1/47 (H1N1, a mouse-adapted strain) albeit the viral titers of these mice showed no difference from those of control mice. There were significantly fewer antigen-specific CD44+ CD8+ T cells in the lungs of infected IL-15 KO mice, and adoptive transfer of the CD8+ T cells caused reduced survival of IL-15 KO mice following influenza virus infection. Mice deficient in β2 -microglobulin by gene targeting and those depleted of CD8+ T cells byin vivo administration of anti-CD8 monoclonal antibody displayed a reduced mortality rate after infection. These results indicate that IL-15-dependent CD8+ T cells are at least partly responsible for the pathogenesis of acute pneumonia caused by influenza A virus.