L Van Bockstal1; P Delputte1; L Maes1; G Caljon1;
1 Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Belgium
DiscussionINTRODUCTION: Type I interferons (IFNs) induced by an endogenous Leishmania RNA virus or exogenous viral infections were shown to exacerbate infections with New World Cutaneous Leishmania parasites. The impact of type I IFNs in visceral Leishmania infections and implicated mechanisms remain to be unraveled. This study assessed the impact of type I IFN on macrophage infection with visceral Leishmania parasites and the implication of sialoadhesin (Siglec-1/CD169, Sn) as a typical IFN-inducible, virus-responsive surface receptor. METHODOLOGY: Bone marrow derived macrophages from wildtype and sialoadhesin knock out (Sn-/-) C57BL/6 mice were collected and cultivated in vitro. Macrophages were stimulated with type I IFN (IFN-a) prior to infection with L. infantum and L. donovani laboratory strains and a set of recent clinical isolates. After two days of stimulation, cells were incubated with an anti-sialoadhesin monoclonal antibody (mAb) or a bivalent nanobody (Biv-Nb). One hour after blocking with the mAb or Biv-Nb, cells were infected with metacyclic promastigotes and parasite multiplication was measured at 48 hours post infection. RESULTS:Stimulation ofbone marrow-derived macrophages with type I IFN (IFN-a) significantly enhanced susceptibility to Leishmania infection. Stimulation experiments in Sn-deficient macrophages and macrophage pretreatment with monoclonal anti-Sn antibodies or bivalent anti-Sn nanobodies restored normal susceptibility levels. Infections with bioluminescent L. infantum promastigotes revealed a moderate role for Sn during visceral infections under the used experimental conditions in vivo. CONCLUSIONS These data indicate that IFN-responsive Sn expression can enhance the susceptibility of macrophages to infection with visceral Leishmania promastigotes and that targeting of Sn may have some protective effects during an early infection.