HIV‐1 gp120 confers a pro‐inflammatory phenotype to macrophages changing the role of the alpha7 acetylcholine receptor

Abstract

Human immunodeficiency virus (HIV‐1) remains a public health threat. The introduction of combined antiretroviral treatments has markedly increase life expectancy but inflammation has remained unsolved. Recent studies, in control subjects, link macrophage's alpha7 nicotinic acetylcholine receptor (α7‐nAChR) activation with anti‐inflammatory response. This response normally prevents exaggerated immune responses through the cholinergic anti‐inflammatory pathway (CAP) which inhibits the release of pro‐inflammatory cytokines through the activation of the α7‐nAChR. Nonetheless, little is known if this neuroimmune regulation is affected in HIV‐1 infected patients. Here we examined the secretion of 9 cytokines and chemokines from control subjects exposed to HIV gp120 envelope protein to determine if the CAP is disrupted. We found that HIV gp120 induce α7‐nAChR upregulation and a pro‐inflammatory phenotype in macrophages as demonstrated by the inability to control the release of 8 of 9 pro‐inflammatory cytokines. These results suggest that HIV mitigates the natural strategy to control inflammation by promoting the upregulation of α7‐nAChR, a key player in the CAP, contributing to one crucial, unresolved problem of HIV infection despite therapy: inflammation. Sponsored by NIH‐NINDS Specialized Neuroscience Program U54NS0430311