Abstract
Leishmaniasis is a vector-borne parasitic disease caused by protozoa of the genus Leishmania. Twenty different species are known to cause disease in humans with varying degrees of pathology. These diseases are transmitted throughout the geographic range of phlebotomine sandflies, found between the latitudes 50°N and 40°S. This study explores antibody dependent enhancement (ADE) as the cause of disease exacerbation in heterologous exposure of L. major primed mice to L. infantum challenge. BALB/c mice received serum from L. major infected or naive mice. All mice were challenged with L. infantum and tissue parasite burdens were recorded. Animals that received anti-L. major serum exhibited significantly higher parasite burdens. Surprisingly, these parasite burdens were higher than those of mice infected with L. major and challenged with L. infantum. In vitro phagocytosis assays were carried out to measure parasite uptake in the presence of naive vs. anti-L. major serum. J774A.1 murine monocytes were cultured with either L. major or L. infantum in the presence of anti-L. major serum, naive serum, or no serum. Significantly higher rates of L. major uptake by J774A.1 cells occurred in the presence of anti-L. major serum, but no measurable increase of L. infantum phagocytosis was seen. Our results suggest that increased disease severity observed in vivo in mice previously exposed to L. major and challenged with L infantum is not a result of extrinsic ADE. We speculate that intrinsic ADE, due to biased memory T cell responses caused by Fcγ signaling, could account for disease exacerbation seen in the animal model.
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Acknowledgements
The authors would like to express their gratitude to Mark Young and Jonathon Betz for their technical assistance and support. We also wish to thank the Central Washington University College of the Sciences for partially funding this research. The work described here formed part of a thesis approved by Central Washington University for a Master of Sciences degree awarded to A. McNolty.
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McNolty, A., Anderson, H., Stryker, G.A. et al. Investigations on the effects of anti-Leishmania major serum on the progression of Leishmania infantum infection in vivo and in vitro – implications of heterologous exposure to Leishmania spp. Parasitol Res 120, 1771–1780 (2021). https://doi.org/10.1007/s00436-021-07130-x
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DOI: https://doi.org/10.1007/s00436-021-07130-x