Researchers here show that blocking increased PGE2 signaling in the aging lung helps to restore resistance to influenza infection. There is an interaction between PGE2, cellular senescence in cells of the alveoli in the lung, and the behavior of local macrophages of the innate immune system. It remains to be seen whether PGE2 signaling is regulating much the same issues connected to cellular senescence elsewhere in the body.
Previous research by another group showed that when macrophages from an old mouse were put into a young mouse, and cells looked young again. Signs pointed to a lipid immune modulator known as prostaglandin E2 (PGE2) with wide ranging effects. The study team discovered there is more PGE2 in the lungs with age. This increase in PGE2 acts on the macrophages in the lung, limiting their overall health and ability to generate. The team suspects that the buildup of PGE2 is yet another marker of a biological process called senescence, which is often seen with age.
The study showed that with age, the cells lining the air sacs in the lungs become senescent, and these cells lead to increased production of PGE2 and suppression of the immune response. To test the link between PGE2 and increased susceptibility to influenza, they treated older mice with a drug that blocks a PGE2 receptor. “The old mice that got that drug actually ended up having more alveolar macrophages and had better survival from influenza infection than older mice that did not get the drug.” The team plans to next investigate the various ways PGE2 affects lung macrophages as well as its potential role in inflammation throughout the body.