Protein preserves delicate balance between immune response and host

"We know that the protein CEACAM1 is involved in the regulation of white blood cells, but its specific role in neutrophil-dependent host immune responses has not been investigated," explains senior study author, Dr. John E. Shively from the Beckman Research Institute of City of Hope in Duarte, California. "We were interested in determining what would happen to neutrophil-mediated immunity in mice that did not express CEACAM1." Dr. Shively and coauthor Dr. Hao Pan found that mice lacking CEACAM1 had an excess number of neutrophils and that CEACAM1 inhibited a specific signaling pathway that is required for white blood cell proliferation.

Interestingly, the excess neutrophils did not provide any additional protection from bacterial infection. In contrast, after infection with Listeria, mice without CEACAM1 died dramatically faster than control mice. The researchers went on to show that the mice lacking CEACAM1 exhibited improved bacterial clearance, but that this was accompanied by severe tissue damage to the liver. The authors concluded that the combination of high levels of neutrophil-secreted chemicals damaged the liver and induced accelerated mortality in Listeria-infected mice lacking CEACAM1. "The insights from our work highlight the importance of natural mechanisms that restrain white blood cell proliferation and may have clinical implications in treating infectious and auto-inflammatory disorders," says Dr. Shively