HIV-infection of the central nervous system: the tightrope walk of innate immunity

Infection of the central nervous system (CNS) by HIV is a frequent and sometimes very early event in the course of HIV pathogenesis. Possible consequences are diverse symptoms of neurological dysfunction, but also the establishment of a lifelong latent viral reservoir in the brain. Whereas in the periphery innate and adaptive immunity are equal partners, the blood-brain barrier (BBB) with its restricted access of peripheral immune effectors shifts this balance in favour of the local innate immunity. Four main elements of cerebral innate immunity are discussed in the present article, including two cell types with immunological functions and two soluble immune systems: (1) the stimulation of microglial cells as the predominant brain-resident immune cell and the main local reservoir for the virus; (2) the reaction of astrocytes in response to viral infection; (3) the activation of the local complement system as important soluble immune cascade; and (4) the role of chemokines and cytokines which help to conduct and cross-link the interplay between the different immune elements. These components of the cerebral innate immunity do not act separately from each other but form a functional immunity network. A dual role of these components with both harmful and protective effects further enhances the complexity of the mutual interactions.