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

Infection is a highly relevant and lethal complication of TBI (1-8). However, there is a relative paucity of data in the literature with regards to traumatic brain injury-induced immune suppression. The proposed study will utilize a murine model of TBI specifically for the study of the peripheral immune sequelae to TBI. Moreover, this will be the first study of its kind to specifically address the role of monocytes and macrophages in driving the pathological immune response to brain injury. Our murine TBI model will allow for a detailed cellular and molecular dissection of the immune pathways involved in this poorly understood injury process. The novel and unique central theme in the current proposal is that monocytes/macrophages initiate the pathogenesis of TBI-induced immune dysfunction by creating and driving a systemic anti-inflammatory milieu. Understanding the nature of this pathogenesis raises the possibility of therapeutically altering monocyte/macrophage phenotype thereby altering the overall immune response to TBI.