To characterize the immune response at the lesional level in patients presenting with cutaneous leishmaniasis (CL) in Ethiopia using spatial transcriptomics.
Approach:
Study Design: Exploratory study using spatial transcriptomics on paired lesional and non-lesional skin punch biopsies from five Ethiopian CL patients.
Methods: Reference-free deconvolution, morphology-guided regional analyses, and immunohistochemistry-based validation were employed to characterize tissue responses.
Key Findings:
Identified spatially distinct immunopathological tissue responses including: i) epithelial hyperplasia with interferon-stimulated keratinocytes, ii) cytotoxicity with tertiary lymphoid structures, iii) granulomatous inflammation with proinflammatory response, iv) granulomatous inflammation with M2-polarised myeloid cell responses, and v) fibrotic remodelling with active collagen synthesis.
Each patient in this case series exemplified one of these tissue responses, but immunopathological features were not mutually exclusive.
This study extends our understanding of Ethiopian CL immunopathology and provides a molecular and cellular context that can be applied in larger clinical cohorts for testing hypotheses regarding the host and/or parasite determinants of CL disease diversity.
Interpretation:
The study provides insights into the immune responses in Ethiopian CL, highlighting the complexity of the disease.
Limitations:
Small sample size of five patients limits generalizability.
Exploratory nature of the study may not capture the full spectrum of immune responses.
Conclusion:
This study enhances the understanding of the immunopathological landscape of cutaneous leishmaniasis in Ethiopia and sets the stage for larger clinical studies.
