Local immune responses to influenza virus infection in mice with a targeted disruption of perforin gene.
The role of perforin in the local defense mechanisms against influenza virus infection was investigated. Mice deficient in the perforin gene (perforin(-/-)) were more susceptible to influenza virus infection than the ordinary wild-type C57BL/6 mice, showing an increased mortality with elevated virus growth and prolonged virus shedding. The lung parenchyma cells of perforin(-/-) mice showed no cytolytic activities of natural killer cells or virus-specific cytotoxic T lymphocytes in vitro, although the local antibody production system in the respiratory tract functioned well. In perforin(-/-) mice, the appearance of apoptotic degeneration in virally infected lung cells was delayed. This might cause cellular infiltration, including CD4, CD8, and CD19 positive cells, in the lung, peaking at day 8 after infection and maintaining a high level for a longer period. In the virus-induced local cytokine production, interferon-gamma (IFN-gamma) was prominent. The adoptive transfer of immune-competent spleen cells from wild-type C57BL/6 mice achieved a complete protection of perforin(-/-) mice against lethal challenge infection. These results suggest that perforin plays a crucial role in the host defense system against influenza virus infection, especially in its early stage, by inducing apoptosis of virus-infected cells.
Liu
Beixing
B
Department of Microbiology, School of Medicine, Fukui Medical University, Shimoaisuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan. liu@fmsrsa.fukui.med.ac.jp
Mori
Isamu
I
Hossain
Md Jaber
MJ
Dong
Li
L
Chen
Zhimin
Z
Kimura
Yoshinobu
Y
D019264:Adoptive Transfer; D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D017201:Virus Shedding
D000914:Antibodies, Viral; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D007371:Interferon-gamma