Interferon Alpha Favors Macrophage Infection by Visceral Leishmania Species Through Upregulation of Sialoadhesin Expression

• Published in: Frontiers in immunology 2020-06, Vol.11, p.1113-1113
• Main Authors: Van Bockstal, Lieselotte, Bulté, Dimitri, Van den Kerkhof, Magali, Dirkx, Laura, Mabille, Dorien, Hendrickx, Sarah, Delputte, Peter, Maes, Louis, Caljon, Guy
• Format: Article
• Language: English
• Subjects: Animals; CD169; Female; IFN-α; Immunology; Interferon-alpha - immunology; Leishmania; Leishmania - immunology; Leishmaniasis, Visceral - immunology; Leishmaniasis, Visceral - metabolism; macrophages; Macrophages - immunology; Macrophages - metabolism; Macrophages - parasitology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Sialic Acid Binding Ig-like Lectin 1 - immunology; Sialic Acid Binding Ig-like Lectin 1 - metabolism; sialoadhesin; type I IFN; Up-Regulation
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.01113

Type I interferons (IFNs) induced by an endogenous RNA virus or exogenous viral infections have been shown to exacerbate infections with New World Cutaneous parasites, however, the impact of type I IFNs in visceral infections and implicated mechanisms remain to be unraveled. This study assessed the impact of type I IFN on macrophage infection with and and 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-α) significantly enhanced susceptibility to infection of reference laboratory strains and a set of recent clinical isolates. IFN-α 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-α. 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 bioluminescent promastigotes 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 visceral promastigotes and that targeting of Sn may have some protective effects in early infection.