MIF expression is involved in the activation of CD4+ T-cells and facilitates the infection by HIV-1

SALIDO JIMENA; TURK GABRIELA; TRIFONE CÉSAR ARIEL; GHIGLIONE YANINA; CZERNIKIER ALEJANDRO

Mar del Plata

Congreso; SAI-SAIC-SAFIS 2018; 2018

SAIC

Macrophage Migration Inhibitory Factor (MIF) plasmalevels are increased in HIV+ individuals compared to healthy donors.Our group described a novel function of MIF in inflammatory processes whenacting on primary HIV-1 infected MDMs. Additional evidence suggests that MIFexpression might play a relevant role in the activation of CD4+ T lymphocytes (CD4TL).Aim: to identify the role of MIF in CD4TL activation and subsequent HIV-1 infection.Primary CD4TL from healthy donors were activatedwith PHA with or without adding a MIF-blocking antibody. Also, the effect ofexogenous-added MIF on not activated CD4TL was assessed. In both conditions, expressionof membrane markers were evaluated by flow cytometry. Permissiveness to HIV-1infection was evaluated. Two reporter lines (CEM and Ghost) were stimulatedwith MIF to evaluate GFP expression downstream the LTR viral promoter.In primary CD4TL, MIF neutralization inhibited PHA-drivenactivation. A decrease in the frequency of blast like cells (16.88%) comparedto PHA-activated CD4TL (50.71%) (p=0.017) was observed. Also, lower expressionof membrane activation markers (CD38, CD28, HLA-DR), was found.Number of infected cells was significantly lower whenblocking MIF activity (1.32%), compared to the PHA-alone control (6.58%, 0.0026),resembling results from not activated CD4TL (0.85%).MIF-stimulated not activated CD4TL showed a higherviral production after infection (95.82 ng/ml) compared to unstimulated cells (11.84ng/ml) (p=0.022). No differences were detected in infection percentage, cell viabilityor activation among all conditions. Finally, LTR promoter-driven expression ofGFP in reporter cell lines was unaffected by MIF. Our work depicts an important role of MIF in CD4TLactivation. Intracellular MIF activity drives CD4TC activation, which in turn,promotes permissiveness to HIV-1 infection. Conversely, exogenous MIF triggeredhigher viral production without affecting cell activation, proliferation or infectionpercentage. These differences could be related to pathway signalling.Intracellular expression could trigger mechanisms unavailable to exogenous MIFdue to a possible low incorporation into the cell.