The central nervous system is a precious and fragile organ, as it is hardly renewable. As a result, it is particularly protected from microorganisms by an anatomical barrier separating the bloodstream from the brain parenchyma. However, there are resident cells within the brain parenchyma that represent a first line of defense in the event of infection: microglia. In addition, all cells in the nervous system are capable of innate immune response. Peripherally, in the perivascular spaces and perivascular lymphatics, lymphocytes and mobilizable dendritic cells circulate. A large number of microorganisms can cause infections of the meningeal compartments, ventricular system and parenchyma, resulting in potentially severe infections and irreversible damage. Pathogens enter either as hosts to myeloid cells, by opening the junction between endothelial cells of the blood-brain barrier, or by infecting these cells. Within the nervous system, microglia cells lining the entire parenchyma detect danger signals associated with the presence of microorganisms via the various innate immunity pathways. Pro-inflammatory and chemoattractant mediators are rapidly produced by macrophages, polymorphs and lymphocytes. We know that innate immunity pathways play a decisive role in the control of certain infections. For example, the pathway induced by nucleic acid recognition by the endosomal receptor TLR3 is essential for controlling infection by the herpes simplex virus.
A major issue in the antipathogenic immune response within the nervous system concerns the possible deleterious consequences of the immune response on the nervous system (NS). We know that many infections of the nervous system - meningitis or encephalitis - are responsible for serious sequelae, partly as a result of the immune response, and the neuronal toxicity of cytokines and products of innate immunity (proteases, cytokines, oxygen radicals). Added to this is the possibility of autoimmune responses, as described in the aftermath of herpes infection, through the production of autoantibodies directed against synaptic receptors, possibly by molecular mimicry. However, during infection control, microglia and macrophages produce a series of molecules which, on the one hand, are anti-inflammatory and, on the other, are involved in repair mechanisms such as axonal regeneration and remyelination. This subtle balance, the regulation of which is still poorly understood, is likely to be compromised in the development of neurodegenerative pathologies.
