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BACKGROUND: Although this seems to be common knowledge among experts, it is important to remind readers that two populations, namely, brain microglia and macrophages, found in different compartments of the central nervous system, play essential roles in innate neuroimmunology. SUMMARY: Here, some historical and conceptual background will be provided that should allow the reader to place recent findings on these cells in some context and perspective. KEY MESSAGES: It will be argued that (1) the brain is not devoid of immune response, but does represent an immune-privileged site, (2) innate neuroimmunology concerns brain border macrophages and parenchymal microglia, (3) even though brain border macrophages have been less extensively studied than parenchymal microglia, it is progressively becoming clear that these populations play different roles in physiological and pathological conditions and (4) while it is tempting to only use the latest technologies to obtain new findings, it is also essential, for the sake of science, to "triangulate" with findings obtained with more classic approaches. To determine whether and when innate neuroimmune responses are protective or pathological will be an important aim for future research.
Jan Pieter Konsman (Wed,) studied this question.