Interferon Alpha Favors Macrophage Infection by Visceral Leishmania Species Through Upregulation of Sialoadhesin Expression
Type I interferons (IFNs) induced by an endogenous Leishmania RNA virus or exogenous viral infections have been shown to exacerbate infections with New World Cutaneous Leishmania parasites, however, 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 L. infantum and L. donovani 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 L. infantum 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 Leishmania promastigotes and that targeting of Sn may have some protective effects in early infection.
CITE THIS COLLECTION
REFERENCES
- https://doi.org//10.1371/journal.pone.0035671
- https://doi.org//10.1016/j.pt.2006.06.012
- https://doi.org//10.1371/journal.pntd.0004904
- https://doi.org//10.1038/nrmicro2608
- https://doi.org//10.1073/pnas.1621447114
- https://doi.org//10.1093/infdis/jiv354
- https://doi.org//10.1007/s00705-016-3044-z
- https://doi.org//10.4269/ajtmh.15-0803
- https://doi.org//10.1093/infdis/jix416
- https://doi.org//10.1038/s41564-018-0352-y
- https://doi.org//10.1126/science.1199326
- https://doi.org//10.3389/fcimb.2012.00099
- https://doi.org//10.1038/nri3581
- https://doi.org//10.1089/jir.2007.0001
SHARE
Usage metrics
Read the peer-reviewed publication
AUTHORS (9)
CATEGORIES
- Transplantation Immunology
- Tumour Immunology
- Immunology not elsewhere classified
- Immunology
- Veterinary Immunology
- Animal Immunology
- Genetic Immunology
- Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)
- Autoimmunity
- Cellular Immunology
- Humoural Immunology and Immunochemistry
- Immunogenetics (incl. Genetic Immunology)
- Innate Immunity