CNS. Brain endothelial cells also express TLR4 and are able to receive neuroimmune stimulation from the brain side and secrete cytokines into the blood or receive stimulation from the blood and secrete cytokines into the brain, suggesting that the blood brain barrier (BBB) may be a fourth component involved in the cross-talk between neurons, microglia, and astrocytes [12]. Further study is needed to determine the exact cellular location of TLR4 in the brain and to decipher the contribution of neurons versus glia in innate immune responses. Nonetheless, the diverse roles of TLRs no doubt depend on the specific TLR, its agonists, mediators, and cellular location.
