Microglia/macrophages in CNS pathology:

Micorglia are essentially indistinguishable from mature tissue macrophages, but have different functional properties. The investigation of the relative role of these inflammatory cell subsets in CNS pathology has been hindered by the fact that the method routinely used for the generation of chimeric mice requires myeloablation by irradiation, which affects the blood-brain barrier, and the forced mobilization and injection in the bloodstream of hematopoietic progenitors that would normally not exit the bone marrow environment. This leads to the artifactual replacement of microglial cells with bone marrow derived cells. We use an alternative method method to generate chimeras which is alternative method to generate chimeras which is based on parabiosis (the surgical joining of two immunocompatible adult mice leading to blood sharing) we were able to show that microglia is capable of self renewing within the CNS and it is not dependent on bone marrow resident hematopoietic stem cells. This finding was later confirmed by others, which showed that microglia originates from yolk sac hematopoiesis early during development, and not from bone marrow hematopoietic stem cells. Taking advantage of this unique system, we have recently shown that blood derived cells infiltrating the CNS cause the progression of EAE, a mouse model of Multiple Sclerosis to paralysis stages. In addition, we also realized that even when bone marrow derived cells enter the CNS they are unable to replace the endogenous microglia, and they eventually disappear 

Ongoing work in the lab addresses questions such as:

What molecular differences allow microglia but not bone marrow derived macrophages to self renew in the CNS? What determines whether innate immune cells cross (e.g. in MS) or not (e.g. following axotomy or in ALS) the blood brain barrier? How do microglia and bone marrow derived myelomonocytic cells change from induction to remission of EAE?