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

TRIFONE, CÉSAR; SALIDO, JIMENA; RUIZ, M.J.; LENG, LIN; BUCALA, RICHARD; SALOMON H; FLORENCIA QUIROGA; GHIGLIONE, Y.; TURK, GABRIELA

Paris

Congreso; IAS 2017; 2017

Background: Understanding the mechanisms involved in HIV-1 infection wouldfacilitate the identification of new therapeutic targets to control the infection inthe face of HAART limitations. CD74 membrane expression is up-regulated ininfected cells during HIV-1 infection and correlates with immune hyperactivationin HIV-infected individuals. Additionally, plasma level of CD74 activating ligandMIF (Macrophage Migration Inhibitory Factor) is increased in infected subjects.However, the role played by MIF/CD74 interaction in HIV pathogenesis remainsunexplored.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 wereinfected, with a R5-tropic HIV-1 virus, and stimulated with MIF concentrationsranging from 1 to 200 ng/ml. Cytokine production and Toll-like receptor 4 (TLR4)expression were measured. Resting CD4TLs were treated with MDM supernatantsor exogenous cytokines to evaluate stimulation of permissiveness to X4-tropic HIV-1infection 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 increasein IL-6, IL-8, TNFα, sCD23 and sICAM production (p=0.006; p=0.013, p=0.0003,p