As functions of reactive astrocytes are elucidated, cumulative evidence points towards reactive astrocytes as integral and essential components of multicellular CNS innate immunity. Astrocytes have long been recognized to respond to activators of innate immune responses [89], including all forms of microbial pathogens [20, 21], environmental toxins [24, 25] and diverse forms of tissue damage as discussed above (Figure 1A). Astrocytes in healthy tissue express many of the receptors to PAMPs and DAMPs known to trigger innate immune responses [90] (Figure 3), in particular TLRs, including TLR4 [90], which is sometimes erroneously attributed only to microglia. Astrocytes exchange molecular signals and interact directly with other innate immune cells such as microglia [91], various perivascular cells and blood borne leukocytes [8, 32]. Astrocytes n both elaborate and respond to a wide variety of cytokines, chemokines, growth factors and other molecules used for inter-cellular communication during innate immune responses, as discussed above (Figure 1). Reactive astrocytes can attract, instruct and corral inflammatory and immune cells (reviewed in detail elsewhere [32]). Multiple genetic deletion studies show that attenuating astrocyte reactivity disrupts CNS innate
