Nature Immunology pp 1037 - 1056

Excessive stimulation of bone marrow stem cells in mice leads to severe anemia and ultimately death, according to research to be published in the October issue of Nature Immunology.

Hematopoietic stem cells residing in the bone marrow give rise to all blood cells circulating in the body. To ensure a lifelong supply of blood cells, these stem cells must continuously self-renew. Previous work revealed stem cells require a signaling molecule called Wnt to activate beta-catenin, a protein involved in self-renewal. Research from two groups shows that excessive beta-catenin signals lead instead to a loss of stem cells and problems in blood cell development. Mice expressing a mutant form of beta-catenin, engineered to be permanently switched on, died at a very young age due to defects in blood cell production. These findings suggest therapeutic manipulation of bone marrow stem cells via Wnt signals to achieve increased blood cell production needs to be finely balanced to avoid too much of a good thing.

Nature Immunology pp 1074 - 1081

A protein called SARM -- SAM and ARM-containing protein -- helps to regulate the immune response against invading pathogens, according to a report in the October issue of Nature Immunology.

SARM is a member of the so-called 'TIR' — Toll-interleukin 1 receptor — adaptor protein family. All other members of this family help to transmit signals triggered by pathogens to promote an immune response. Andrew Bowie and colleagues now show that in contrast to the other four members of the TIR family, SARM unexpectedly blocks rather than promotes signals triggered by pathogens. The identification of SARM as a regulator, rather than a promoter, of the immune response may prove useful therapeutically.

Nature Immunology pp 1066 - 1073

An effective way to vaccinate against infection by the plague bacterium Yersinia pestis in mice is reported in a study to be published in the October issue of Nature Immunology. This organism has been a scourge of humans for hundreds of years.

Egil Lien and colleagues have taken advantage of the fact that bacteria like Y. pestis 'wear a coat' of protein and fatty sugars. The 'coats' of some bacteria normally stimulate mammalian immune cells, whereas others, such as those of Y. pestis, do not, allowing them to evade or suppress the innate immune response of the host. Lien and colleagues have engineered a Y. pestis strain with a coat that stimulates immune cells in mice, and show that mice can survive infection with this engineered strain. The mice also appear to be protected from subsequent infection with normal, otherwise deadly, Y. pestis.

The authors propose that their work, which demonstrates that sufficient stimulation of innate immune responses can control infection by a highly virulent pathogen, has broad implications for understanding bacterial virulence in Y. pestis, and also for potential strategies for vaccine production.