Enhancement of HIV-1 spreading and persistence by MIF/CD74 interaction in primary monocyte-derived macrophages (MDM) and CD4+ T-lymphocytes (CD4TL) in vitro

M.J. RUIZ; H. SALOMON; G. TURK; J. SALIDO; R. BUCALA; Y. GHIGLIONE; C. TRIFONE; L. LENG; F. QUIROGA

Paris

Conferencia; IAS 2017 - 9th IAS Conference on HIV Science; 2017

International AIDS Society

Background: Understanding the mechanisms involved in HIV-1 infection would facilitate the identification of new therapeutic targets to control the infection in the face of HAART limitations. CD74 membrane expression is up-regulated in infected cells during HIV-1 infection and correlates with immune hyperactivation in HIV-infected individuals. Additionally, plasma level of CD74 activating ligand MIF (Macrophage Migration Inhibitory Factor) is increased in infected subjects. However, the role played by MIF/CD74 interaction in HIV pathogenesis remains unexplored. Aim: to study the effect of MIF/CD74 interaction in primary HIV-infected monocyte-derived macrophages (MDMs) and CD4+ T-lymphocytes (CD4TLs).Methods: CD4TL and MDMs were obtained from healthy donors. MDMs were infected, with a R5-tropic HIV-1 virus, and stimulated with MIF concentrations ranging from 1 to 200 ng/ml. Cytokine production and Toll-like receptor 4 (TLR4) expression were measured. Resting CD4TLs were treated with MDM supernatants or exogenous cytokines to evaluate stimulation of permissiveness to X4-tropic HIV-1 infection by p24 quantitation. Cell death was measured by flow cytometry in infected and MIF-treated CD4TLs. Data analysis was performed by parametric methods.Results: Treatment of infected MDMs with MIF resulted in a dose-dependent increase in IL-6, IL-8, TNFα, sCD23 and sICAM production (p=0.006; p=0.013, p=0.0003, p