Interferon alpha favors macrophage infection by visceral leishmania species through upregulation of sialoadhesin expression

Type I interferons (IFNs) induced by an endogenousLeishmaniaRNA virus or exogenous viral infections have been shown to exacerbate infections with New World CutaneousLeishmaniaparasites, however, the impact of type I IFNs in visceralLeishmaniainfections and implicated mechanisms remain to be unraveled. This study assessed the impact of type I IFN on macrophage infection withL. infantumandL. donovaniand the implication of sialoadhesin (Siglec-1/CD169, Sn) as an IFN-inducible surface receptor. Stimulation of bone marrow-derived macrophages with type I IFN (IFN-alpha) significantly enhanced susceptibility to infection of reference laboratory strains and a set of recent clinical isolates. IFN-alpha particularly enhanced promastigote uptake. Enhanced macrophage susceptibility was linked to upregulated Sn surface expression as a major contributing factor to the infection exacerbating effect of IFN-alpha. Stimulation experiments in Sn-deficient macrophages, macrophage pretreatment with a monoclonal anti-Sn antibody or a novel bivalent anti-Sn nanobody and blocking of parasites with soluble Sn restored normal susceptibility levels. Infection of Sn-deficient mice with bioluminescentL. infantumpromastigotes revealed a moderate, strain-dependent role for Sn during visceral infection under the used experimental conditions. These data indicate that IFN-responsive Sn expression can enhance the susceptibility of macrophages to infection with visceralLeishmaniapromastigotes and that targeting of Sn may have some protective effects in early infection.

Publication year:2020

Keywords:A1 Journal article

BOF-keylabel:yes

BOF-publication weight:2

CSS-citation score:1

Authors from:Higher Education

Accessibility:Open