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bioRxiv · 10.1101/2022.06.16.496495

Cytokine and phenotypic cell profiles in human cutaneous leishmaniasis caused by Leishmania donovani

Samaranayake, N.·Wijesooriya, H.·Karunaweera, N. D.
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Abstract

BackgroundThe innate immune mediators are likely to influence the clinical phenotype of leishmaniasis by primary responses which limit or facilitate the spread of the parasite, as well as by modulating adaptive immunity. This study investigated the response of key innate immune cells in a focus which regularly reports localised cutaneous leishmaniasis (LCL) caused by Leishmania donovani, a species which typically causes visceral disease. MethodsPeripheral blood mononuclear cell (PBMC) derived macrophage and dendritic cell responses to soluble Leishmania antigen (SLA) were compared between patients with LCL and healthy controls from endemic and non-endemic areas. Inflammatory mediators produced by macrophages (TNF-, NO, TGF-{beta} and IL-10) and dendritic cells (IL-12p70, IL-10) and cell surface markers of macrophage polarization, activation and maturation were determined at 24h, 48h and 72h by Enzyme-linked immunosorbent assay (ELISA) and flowcytometry. ResultsPatient derived macrophages and dendritic cells produced higher levels of both pro and anti-inflammatory mediators compared to controls (p<0.05) with the best discrimination for active disease observed at 72h. Data demonstrated an early activation of macrophages and a subsequent pro-inflammatory bias, as indicated by temporal profiles of TNF-/TGF-{beta} and TNF-/IL-10 ratios and higher proportions of classical (M1) macrophages. Higher TGF-{beta} levels were observed in cells from patients with ulcerated or persistent lesions. Immune responses by cells derived from controls in endemic and non-endemic regions did not differ significantly from each other. ConclusionsThe overall immunophenotypic profile suggests that LCL observed in the country is the result of a balancing immune response between pro-inflammatory and regulatory mediators. The mediators which showed distinct profiles in patients warrant further investigation as potential candidates for immunotherapeutic approaches. A comparison with visceral leishmaniasis caused by the same species, would provide further evidence on the differential role of these mediators in the resulting clinical phenotype.

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Samaranayake, N., Wijesooriya, H., Karunaweera, N. D.. 2022-06-17. Cytokine and phenotypic cell profiles in human cutaneous leishmaniasis caused by Leishmania donovani. https://doi.org/10.1101/2022.06.16.496495

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