Spontaneous Neutrophil Activation in HTLV-1 Infected Patients

Abstract

Human T cell lymphotropic Virus type-1 (HTLV-1) induces lymphocyte activation and proliferation, but little is known about the innate immune response due to HTLV-1 infection. We evaluated the percentage of neutrophils that metabolize Nitroblue tetrazolium (NBT) to formazan in HTLV-1 infected subjects and the association between neutrophil activation and IFN-γ and TNF- α levels. Blood was collected from 35 HTLV-1 carriers, from 8 patients with HAM/TSP (HTLV-1- associated myelopathy); 22 healthy individuals were evaluated for spontaneous and lipopolysaccharide (LPS)-stimulated neutrophil activity (reduction of NBT to formazan). The production of IFN-γ and TNF-α by unstimulated mononuclear cells was determined by ELISA. Spontaneous NBT levels, as well as spontaneous IFN-γ and TNF-α production, were significantly higher (p<0.001) in HTLV-1 infected subjects than in healthy individuals. A trend towards a positive correlation was noted, with increasing percentage of NBT positive neutrophils and levels of IFN-γ. The high IFN-γ producing HTLV-1 patient group had significantly greater NBT than healthy controls, 43+24% and 17+4.8% respectively (p< 0.001), while no significant difference was observed between healthy controls and the low IFN-γ-producing HTLV-1 patient group (30+20%). Spontaneous neutrophil activation is another marker of immune perturbation resulting from HTLV-1 infection. In vivo activation of neutrophils observed in HTLV-1 infected subjects is likely to be the same process that causes spontaneous IFN-γ production, or it may partially result from direct IFN-γ stimulation.