Article ; Online: Cytokine and phenotypic cell profiles in human cutaneous leishmaniasis caused by Leishmania donovani.
2023 Volume 18, Issue 1, Page(s) e0270722
Abstract: Background: The 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 ... ...
| Abstract | Background: The 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. Methods: Peripheral blood mononuclear cell (PBMC) derived macrophages and dendritic cells from patients with LCL and healthy controls from endemic and non-endemic areas, were stimulated with soluble Leishmania antigen (SLA). Inflammatory mediators produced by macrophages (TNF-α/TGF-β/IL-10, ELISA; NO, Griess method) and dendritic cells (IL-12p70, IL-10, flowcytometry) and macrophage expression of surface markers of polarization, activation and maturation (flowcytometry) were determined at 24h, 48h and 72h and compared. Study was conducted prospectively from 2015-2019. Results: Patient 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-α/TGF-β and TNF-α/IL-10 ratios and higher proportions of classical (M1) macrophages. Higher TGF-β 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. Conclusions: The 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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| MeSH term(s) | Humans ; Cytokines/metabolism ; Leishmania donovani ; Interleukin-10/genetics ; Leukocytes, Mononuclear/metabolism ; Tumor Necrosis Factor-alpha/genetics ; Leishmaniasis, Visceral/parasitology ; Leishmaniasis, Cutaneous ; Transforming Growth Factor beta/genetics ; Phenotype |
| Chemical Substances | Cytokines ; Interleukin-10 (130068-27-8) ; Tumor Necrosis Factor-alpha ; Transforming Growth Factor beta |
| Language | English |
| Publishing date | 2023-01-05 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural |
| ZDB-ID | 2267670-3 |
| ISSN | 1932-6203 ; 1932-6203 |
| ISSN (online) | 1932-6203 |
| ISSN | 1932-6203 |
| DOI | 10.1371/journal.pone.0270722 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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