Innate immune response to influenza A virus in differentiated human alveolar type II cells

Jieru Wang, Mrinalini P. Nikrad, Tzulip Phang, Bifeng Gao, Taylor Alford, Yoko Ito, Karen Edeen, Emily A. Travanty, Beata Kosmider, Kevan Hartshorn, Robert J. Mason

研究成果: Article査読

76 被引用数 (Scopus)

抄録

Alveolar Type II (ATII) cells are important targets for seasonal and pandemic influenza. To investigate the influenza-induced innate immune response in those cells, we measured the global gene expression profile of highly differentiated ATII cells infected with the influenzaAvirus at a multiplicity of infection of 0.5 at 4 hours and 24 hours after inoculation. Infection with influenza stimulated a significant increase in the mRNA concentrations of many host defense-related genes, including pattern/pathogen recognition receptors, IFN, and IFN-induced genes, chemokines, and suppressors of cytokine signaling.Weverified these changes by quantitative real-time RT-PCR. At the protein level, we detected a robust virus-induced secretion of the three glutamic acid-leucine-arginine (ELR)-negative chemokines CXCL9, CXCL10, and CXCL11, according to ELISA. The ultraviolet inactivation of virus abolished the chemokine and cytokine response. Viral infection did not appear to alter the differentiation of ATII cells, as measured by cellular mRNA and concentrations of surfactant proteins. However, viral infection significantly reduced the secretion of surfactant protein (SP)-A and SP-D. In addition, influenza A virus triggered a time-dependent activation of phosphatidylinositol 3-kinase signaling in ATII cells. The inhibition of this pathway significantly decreased the release of infectious virus and the chemokine response, but did not alter virusinduced cell death. This study provides insights into influenzainduced innate immunity in differentiated human ATII cells, and demonstrates that the alveolar epithelium is a critical part of the initial innate immune response to influenza.

本文言語English
ページ(範囲)582-591
ページ数10
ジャーナルAmerican journal of respiratory cell and molecular biology
45
3
DOI
出版ステータスPublished - 2011 9 1

ASJC Scopus subject areas

  • 分子生物学
  • 呼吸器内科
  • 臨床生化学
  • 細胞生物学

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