A coat of many colors: neuroimmune crosstalk in human immunodeficiency virus infection

Abstract

The use of antiretroviral therapy has reduced mortality and increased the quality of life of HIV-1-infected people, particularly in more developed countries where access to treatment is more widespread. However, morbidities continue, which include HIV-1-associated neurocognitive disorders (HAND). Subtle cognitive abnormalities and low-level viral replication underlie disease. The balance between robust antiviral adaptive immunity, neuronal homeostatic mechanisms, and neuroprotective factors on one hand and toxicities afforded by dysregulated immune activities on the other govern disease. New insights into the pathobiological processes for neuroimmune-linked disease and ways to modulate such activities for therapeutic gain are discussed. Better understanding of the complexities of immune regulation during HAND can improve diagnosis and disease outcomes but is also relevant for the pathogenesis of a broad range of neurodegenerative disorders.

Figure 1. Neuropathogenesis of HIV-1 Infection

A schematic of the cascade of neuropathologic events during progressive HIV-1 infection of the CNS. Activated monocytes are drawn to the brain by chemokines. CNS infection serves to activate astrocytes and resident microglia leading resulting in spread of infection to neighboring cells with concomitant neuroinflammation. Upon activation microglia polarize to either an M1 or M2 phenotype, leading to a neurotoxic or neurotrophic microglial phenotype during HIV-1 infection of the CNS.

Figure 2. Innate and Adaptive Immunity in HIV-1 Neuropathogenesis

Within the infected brain, both proinflammatory (Teff, CTL, M1 microglia) and protective (M2 microglia, Treg) aspects of immunity are evident [adapted from (Huang et al., 2009)]. When the inflammatory environment becomes dominant disease is manifest.