Abstract
Leishmania braziliensis infection causes skin ulcers, typically found in localized cutaneous leishmaniasis (LCL). This tissue pathology associates with different modalities of cell necrosis, which are subverted by the parasite as a survival strategy. Herein we examined the participation of necroptosis, a specific form of programmed necrosis, in LCL lesions and found reduced RIPK3 and PGAM5 gene expression compared to normal skin. Assays using infected macrophages demonstrated that the parasite deactivates both RIPK3 and MLKL expression and that these molecules are important to control the intracellular L. braziliensis replication. Thus, LCL-related necroptosis may be targeted to control infection and disease immunopathology.
Highlights
Localized cutaneous leishmaniasis (LCL) exhibits significant disease burden in tropical regions worldwide and is characterized by one or more well-limited ulcers with raised borders
To characterize the necroptosis signaling pathway expressed in situ during localized cutaneous leishmaniasis (LCL), we analyzed targeted RNA transcripts isolated from skin biopsy specimens
The reduced expression of RIPK3 found in LCL patients skin lesions suggests that L. braziliensis inhibits its expression to subvert necroptosis
Summary
Localized cutaneous leishmaniasis (LCL) exhibits significant disease burden in tropical regions worldwide and is characterized by one or more well-limited ulcers with raised borders. We performed an exploratory study in patients with LCL from an endemic area in Brazil, assessing in situ RNA expression of targets from the necroptosis pathway. Patients with LCL exhibited substantial reduction in expression of RIPK3 and PGAM5 compared with those from normal skin (Figure 1A).
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