CCL5-CCR5 interaction provides antiapoptotic signals for macrophage survival during viral infection

Nature Medicine 11, 1180 - 1187 (2005)

Speaker：黃炫榕                         Time：15:10 ~ 16:00, Dec. 7, 2005

Commentator：劉校生 老師                Place：Room 601

Abstract:

    During host defense against viral infection, macrophages play a role in clearing cellular corpses of infected cells. Preventing the death of the macrophage allows the host to ultimately clear the cellular debris and finally halt the infection. In this study, the authors investigated how macrophages keep from succumbing to the infection. The results demonstrate that Ccl5^-/- and Ccr5^-/- mice show lower survival rate than wild type mice after Sendai virus (SeV) infection. CCL5 deficiency leads to macrophages reduction in the airspace and accumulated in epithelium at 8-9 days post infection because macrophages were infected with virus and undergoing apoptosis. Thus, CCL5 provides a protective effect against virus-induced apoptosis. Furthermore, CCL5 and its receptor CCR5 interaction turns on bilateral activation of G_αi-PI3K-AKT and G_αi-MEK-ERK signaling pathways. The antiapoptotic pathways allow cells to escape virus-induced death. They also found that the macrophage-deficient mice show reduced the ability of clearing infected cells and concomitantly decreased in survival rate after viral infection. Therefore, the macrophages use CCL5 to ensure that the infection process can be stopped before it goes any further. The information about the role of CCL5 may leads to new methods to hasten recovery from respiratory viral infections like influenza or the common cold.

References:

1.      Tyner, J.W. et al. CCL5-CCR5 interaction provides antiapoptotic signals for macrophage survival during viral infection. Nat. Med. 11, 1180 - 1187 (2005).

2.      Doherty, P.C. & Christensen, J.P. Accessing complexity: the dynamics of virus-specific T cell responses. Annu. Rev. Immunol. 18, 561–592 (2000).