Innate immune responses during neuronal death and regeneration

[Truncated abstract] Trauma to the central nervous system (CNS) results in immediate local cell death and axonal damage at the site of impact. The poor environment around the lesion site triggers a cascade of events, including a large inflammatory response that exacerbates tissue damage. This so-called process of secondary degeneration is thought to ultimately lead to a worsened prospect for functional recovery. As the CNS is generally thought to lack the ability of self-repair, any acquired damage is considered irreversible. Development of therapeutic strategies that can reduce secondary damage is thus of vast importance to prevent additional tissue loss and improve outcomes. Treatment with anti-inflammatory drugs following neurotrauma does not always translate into an improved outcome for patients, suggesting that some aspects of the inflammatory response may be beneficial as part of the wound healing process. Macrophages are cells of the innate immune system that can mediate both inflammation and tissue repair processes in many peripheral organs. However, much less is known on the role of these cells in context of the CNS where mostly injurious roles have been highlighted as part of secondary immunopathology following neurotraumic events. The molecular mechanisms that control recruitment and activation profiles of blood-derived monocytes / macrophages are also poorly understood. The chemokine receptor CX3CR1 is expressed by all cells of monocytic origin. The only known ligand for this receptor is fractalkine/CX3CL1, which can be secreted by neurons and thus provide a link for direct communication between the nervous system and the immune system. Upon activation by fractalkine, CX3CR1 has been shown to induce an anti-inflammatory profile in receptor-bearing cells in vitro as well as in neurodegenerative diseases in vivo.