A critical role for the sphingosine analog AAL-R in dampening the cytokine response during influenza virus infection

作者：Marsolais David; Hahm Bumsuk; Walsh Kevin B; Edelmann Kurt H; McGavern Dorian; Hatta Yasuko; Kawaoka Yoshihiro; Rosen Hugh^*; Oldstone Michael B A

来源：Proceedings of the National Academy of Sciences of the United States of America, 2009, 106(5): 1560-1565.

DOI：10.1073/pnas.0812689106

• immunopathology
• dendritic cells
• cytokine storm
• T cells

Pulmonary tissue damage resulting from influenza virus infection is caused by both the cytolytic activity of the virus and the host immune response. Immune-mediated injury results from T cell-mediated destruction of virus-infected cells and by release of cytokines and chemokines that attract polymorphonuclear leukocytes (PML) and macrophages to the infected site. The cytokines/chemokines potentiate dendritic cell (DC) activation and T cell expansion, which further enhances local damage. Here we report that immune modulation by local administration to the respiratory tract of sphingosine analog AAL-R significantly dampens the release of cytokines and chemokines while maintaining protective neutralizing antibody and cytotoxic T cell responses. As a result there was a marked reduction of infiltrating PML and macrophages into the lung and resultant pulmonary tissue injury. DC maturation was suppressed, which limited proliferation of specific antiviral T cells in the lung and draining lymph nodes. Further, AAL-R was effective in controlling CD8( ) T cell accumulation in the lungs even when given 4 days after initiation of influenza virus infection. These data indicate that sphingosine analogs display useful potential for controlling the immunopathology caused by influenza virus.

• 出版日期2009-2-3
• 单位河北医科大学