Loss of intraepidermal nerve fiber density during SIV peripheral neuropathy is mediated by monocyte activation and elevated monocyte chemotactic proteins

• DOI: 10.1186/s12974-015-0456-8
• Publication Date: 2015-12-18T05:14:06Z
• Authors: Jessica R. Lakritz; Jake A. Robinson; Michael J. Polyde...; Andrew D. Miller; Tricia H. Burdo
• Keywords: Monocyte

Peripheral neuropathy (PN) continues to be a major complication of human immunodeficiency virus (HIV) infection despite successful anti-retroviral therapy. Human HIV-PN can recapitulated in CD8-depleted, simian (SIV)-infected rhesus macaque animal model, characterized by loss intraepidermal nerve fiber density (IENFD) and damage the dorsal root ganglia (DRG). Increased monocyte traffic DRG has previously been associated with severe pathology, as well IENFD. Here, we sought characterize molecular signals activation trafficking DRGs. Eleven SIV-infected CD8-depleted macaques were compared four uninfected control animals. sCD14, sCD163, sCD137, regulated on normal T cell expressed secreted (RANTES), chemoattractant protein 1 (MCP-1) measured plasma latter three proteins also quantified tissue lysates. All animals received serial skin biopsies measure IENFD BrdU inoculations turnover during course infection. The number BrdU+ CD14+ CD16+ peripheral blood monocytes was determined flow cytometry. MAC387+, CCR2+, CCR5+, CD137+ cells immunohistochemistry. MCP-1, sCD137 increased significantly from pre-infection necropsy. Plasma sCD163 RANTES inversely correlated Additionally, lysate elevated pathology recruitment MAC387+ DRG. Elevated numbers CCR5+ CCR2+ satellite found, suggesting chemotactic role their ligands, RANTES, MCP-1 recruiting tissue. We systemic (plasma) tissue-specific (DRG) cytokines pathogenesis SIV-PN. identified potential biomarkers for HIV-PN, these CD137 signaling play possibly contribute pathology. These studies highlight SIV-PN, while identifying specific future pharmacological blockade.