A TRIFfic perspective on acute lung injury

Abstract

Acute lung injury (ALI) is a leading cause of death in people infected with H5N1 avian influenza virus or the SARS-coronavirus. Imai et al. (2008) now report that ALI is triggered by the signaling of oxidized phospholipids through Toll-like receptor 4 (TLR4) and the adaptor protein TRIF. These findings provide insight into the molecular pathogenesis of ALI, a condition for which treatment options are currently very limited.

Figure 1

Oxidized Phospholipids and Acute Lung Injury The work of Imai et al. (2008) provides evidence that acute lung injury involves oxidized phospholipids acting through Toll-like receptor 4 (TLR4). In this model, injury to the lungs through acid aspiration or viral infection leads to activation of NADPH oxidase (NADPH Ox) and production of reactive oxygen species (ROS), which oxidize 1-palmitoyl-2-arachidonoyl-phosphatidylcholine (PAPC, OxPAPC). OxPAPC activates TLR4 expressed by myeloid cells (an alveolar macrophage is shown), and the intracellular signal is transduced by the adaptor proteins TRIF and TRAF6, leading to interleukin 6 (IL-6) production, inflammation, and alveolar damage. PMN, polymorphonuclear leukocyte.