Influenza leaves a TRAIL to pulmonary edema
Rena Brauer, Peter Chen
Rena Brauer, Peter Chen
Published April 1, 2016; First published March 21, 2016
Citation Information: J Clin Invest. 2016;126(4):1245-1247. https://doi.org/10.1172/JCI86802.
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Commentary

Influenza leaves a TRAIL to pulmonary edema

Abstract

Influenza infection can cause acute respiratory distress syndrome (ARDS), leading to poor disease outcome with high mortality. One of the driving features in the pathogenesis of ARDS is the accumulation of fluid in the alveoli, which causes severe pulmonary edema and impaired oxygen uptake. In this issue of the JCI, Peteranderl and colleagues define a paracrine communication between macrophages and type II alveolar epithelial cells during influenza infection where IFNα induces macrophage secretion of TRAIL that causes endocytosis of Na,K-ATPase by the alveolar epithelium. This reduction of Na,K-ATPase expression decreases alveolar fluid clearance, which in turn leads to pulmonary edema. Inhibition of the TRAIL signaling pathway has been shown to improve lung injury after influenza infection, and future studies will be needed to determine if blocking this pathway is a viable option in the treatment of ARDS.

Authors

Rena Brauer, Peter Chen

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Figure 1

Regulation of alveolar water clearance.

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Regulation of alveolar water clearance. (A) Under homeostatic conditions...
(A) Under homeostatic conditions, ENaC and Na,K-ATPase pumps on the alveolar epithelial cells work in conjunction to move sodium out of the alveolus. The osmotic gradient causes water to passively exit the alveolus paracellularly and through aquaporin channels. (B) Influenza infection induces type I IFN expression that stimulates macrophages to secrete TRAIL, which in turn signals endocytosis of Na,K-ATPase in uninfected alveolar epithelial cells. The diminished sodium transport decreases alveolar fluid clearance and contributes to the development of pulmonary edema during influenza infection.