SH3GLB2/endophilin B2 regulates lung homeostasis and recovery from severe influenza A virus infection

Kristin K. Fino, Linlin Yang, Patricia Silveyra, Sanmei Hu, Todd M. Umstead, Susan Diangelo, E. Scott Halstead, Timothy K. Cooper, Thomas Abraham, Yoshinori Takahashi, Zhixiang Zhou, Hong Gang Wang, Zissis C. Chroneos

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

New influenza A viruses that emerge frequently elicit composite inflammatory responses to both infection and structural damage of alveolar-capillary barrier cells that hinders regeneration of respiratory function. The host factors that relinquish restoration of lung health to enduring lung injury are insufficiently understood. Here, we investigated the role of endophilin B2 (B2) in susceptibility to severe influenza infection. WT and B2-deficient mice were infected with H1N1 PR8 by intranasal administration and course of influenza pneumonia, inflammatory, and tissue responses were monitored over time. Disruption of B2 enhanced recovery from severe influenza infection as indicated by swift body weight recovery and significantly better survival of endophilin B2-deficient mice compared to WT mice. Compared to WT mice, the B2-deficient lungs exhibited induction of genes that express surfactant proteins, ABCA3, GM-CSF, podoplanin, and caveolin mRNA after 7 days, temporal induction of CCAAT/enhancer binding protein CEBPα, β, and δ mRNAs 3-14 days after infection, and differences in alveolar extracellular matrix integrity and respiratory mechanics. Flow cytometry and gene expression studies demonstrated robust recovery of alveolar macrophages and recruitment of CD4+ lymphocytes in B2-deficient lungs. Targeting of endophilin B2 alleviates adverse effects of IAV infection on respiratory and immune cells enabling restoration of alveolar homeostasis.

Original languageEnglish (US)
Article number7262
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

All Science Journal Classification (ASJC) codes

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