Lung epithelial apoptosis in influenza virus pneumonia: the role of macrophage-expressed TNF-related apoptosis-inducing ligand

Herold, S. et al. J Exp Med. 205, 3065-3077 (2008)

Speaker: 盧怡恬                                         Time: 15:10~16:00, Mar. 18, 2009

Commentator: 林秋烽 老師                                Place: Room 601

Abstract:

        Influenza virus (IV) is a RNA virus causing infection of the upper and lower respiratory tract. Primary viral pneumonia is the most severe complication observed during IV infection and reveals high mortality.¹ During IV infection, peripheral blood monocytes are recruited to the alveolar compartment of the lung via the interaction of CC-chemokine ligand 2 (CCL2), which is released from alveolar epithelial cells  (AECs) with its monocytic receptor CC-chemokine receptor 2 (CCR2).² Although mononuclear phagocytes play an essential role in the host defense, these cells have been proposed to cause an imbalanced immune response during IV pneumonia and have been implicated in alveolar epithelial damage. The molecular cross-talk between macrophages and epithelial cells is largely unknown. In this study, the authors tested the hypothesis that exudate macrophages, which were recruited to the lung in a CCL2/CCR2-dependent manner, might contribute to lung barrier dysfunction during lethal IV infection. They found that CCR2 deficiency was associated with increased mouse survival and attenuated alveolar leakage. They also observed that alveolarmacrophage recruitment was CCR2-dependent. Furthermore, the accumulation of exudate macrophages in the lung was correlated with AEC apoptosis. After analyzing several proapoptotic factors, they found that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA was up-regulated in exudate macrophages as compared with peripheral blood monocytes. Finally, abrogation of TRAIL signaling in the exudate macrophages decreased AEC apoptosis, attenuated alveolar leakage, and enhanced survival rate after IV infection. Collectively, these results demonstrate that macrophage recruitment to IV-infected lung affects lung barrier function via TRAIL-induced epithelial cell apoptosis.

References:

1.          Cox, N. J. et al. Influenza. Lancet. 354, 1277-1284 (1999).

2.          Herold, S. et al. Alveolar epithelial cells direct monocyte transepithelial migration upon influenza virus infection: impact of chemokines and adhesion molecules. J. Immunol. 177, 1817-1824 (2006).