Jpn. J. Infect. Dis., 64 (6), 451-457, 2011

To see a printable version of the article in the Adobe file format, click this [PDF] link.

Original Article

Increase of Apoptosis in a Murine Model for Severe Pneumococcal Pneumonia during Influenza A Virus Infection

Kosuke Kosai1, Masafumi Seki1,2*, Akitaka Tanaka1, Yoshitomo Morinaga1, Yoshifumi Imamura1, Koichi Izumikawa1, Hiroshi Kakeya1, Yoshihiro Yamamoto1, Katsunori Yanagihara1, Kazunori Tomono2, and Shigeru Kohno1

1Second Department of Internal Medicine, Nagasaki University, Nagasaki 852-8501; and 2Division of Infectious Diseases and Prevention, Osaka University Hospital, Suita 565-0871, Japan

(Received May 6, 2011. Accepted August 17, 2011)

*Corresponding author: Mailing address: Division of Infectious Diseases and Prevention, Osaka University Hospital, Suita City 565-0871, Japan. Tel: +81 6 6879 5093, Fax: +81 6 6879 5094, E-mail:

SUMMARY: The mechanisms of severe pneumonia caused by co-infection of bacteria and influenza A virus (IAV) have not been fully elucidated. We examined apoptosis and inflammatory responses in a murine model for pneumococcal pneumonia during IAV infection. Inflammation, respiratory epithelium apoptosis, and inflammatory-cell infiltration increased in a time dependent manner in the lungs of mice co-infected with Streptococcus pneumoniae and IAV, in comparison with those infected with either S. pneumoniae or IAV. According to appearance of terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling positive cells, caspases-3 and -8 were activated 24 h after S. pneumoniae infection, and caspase-3 activation decreased after 48 h, whereas inflammatory cytokine levels continued to increase in co-infected mice. In contrast, in mice infected with either IAV or S. pneumoniae, apoptosis and activation of factors related to caspase-3 peaked at 48 h. Furthermore, Fas-associated death domain was significantly expressed in the lungs of co-infected mice 24 h after S. pneumoniae infection. These data suggest that early onset of apoptosis and its related factors play important roles in fulminant pneumonia resulting from bacterial pneumonia complicated by co-infection with influenza virus.

Go to JJID Home

Go to JJID 64 (6) Contents