within the perivascular space when blood-borne leukocytes cross the endothelial BBB to gain entry into perivascular spaces in human co-culture models [93]. Astrocytes can also produce multiple cytokines and chemokines capable of recruiting and instructing lymphocytes, suggesting that astrocyte borders around such cuffs may serve to attract and then restrict the spread of blood borne immune and inflammatory cells [32, 81]. Adventitial cuffs of antibody-producing B cells are formed during CNS viral infections, and local antibody production represents an important means of clearing viral infections that is regulated at least in part, by INFγ and IL10 signaling in mouse models of alphaviral encephalomyelitis infection [95–97]. Reactive astrocytes can produce both INFγ and IL10 as well as other B cell attracting chemokines (Figure 1B) [32] and it will be interesting to study potential astrocyte roles in this process. Another relevant aspect of astrocyte reactivity might involve priming to alter innate immune responses to future potential insults as part of what is becoming known as innate immune memory that can be orchestrated by chromatin modification and epigenetic reprogramming [98]. Thus, multiple new roles for astrocytes are emerging in multicellular CNS innate immune responses that merit further investigation.
