Unexpectedly, the investigators found that CCL5 turns on signals that allow cells to escape virus-induced death. These signals are termed anti-apoptotic because they work against a process of programmed cell death called apoptosis. The CCL5-induced anti-apoptotic signals therefore help keep macrophages alive, which allows them to continue their job in the face of a viral onslaught.
"CCL5's role is somewhat of a paradox," Holtzman says. "Ordinarily, apoptosis is a protective mechanism. Death of infected lung airway lining cells, or epithelial cells, would deprive the virus of its home and protect the host against the spread of infection. But in the case of the macrophage, it is the opposite. Preventing the death of the macrophage allows the host to ultimately clear the viral debris and so finally halt the infection. Balancing these cell death and survival pathways can determine whether the virus or the host wins the battle."
Next, the researchers will look further at precisely how CCL5 prevents cell death.
"In this initial study, we identified the cellular receptor for CCLR and some of the first downstream signals that convey a survival message," Holtzman says. "Now, we aim to define more specific signaling proteins that allow the cell to live or die in the face of infection. Identifying these signals may allow us to regulate these signals during an infection, and so make epithelial cells and macrophages more effective to shorten recovery time or lessen symptoms."
The ability to decrease the severity of lung infections may also have important implications for asthma, COPD (chronic obstructive pulmonary disease) and other chronic lung diseases, according to Holtzman.
"We commonly see children, for example, who develop these same types of severe respirato
Source:Washington University School of Medicine