The role of innate immunity in the traumatic brain injury-induced immune suppression syndrome

In order to identify new interventions it is critically important that we increase our understanding of the link between TBI and immune function. We have generated a clinically applicable murine model of TBI for the interrogation of the immune response to TBI. The brain-injured mice display a striking loss of cells from the innate immune system both acutely and chronically. Most notably, there is a rapid and sustained loss of classical and non-classical monocytes in the blood, as early as 24 hours post injury and lasting up to two months post injury. This peripheral loss coincides with a significant infiltration of monocytes and macrophages within the injured brain. Furthermore, we observed a significant shift of these monocytes towards the anti-inflammatory M2 phenotype after injury. Taken together, we hypothesize that monocytes/macrophages initiate the pathogenesis of TBI-induced immune dysfunction by creating and driving a systemic anti-inflammatory milieu resulting in increased infectious mortality after TBI.