In Skin Biopsies of Localized Cutaneous Leishmaniasis Patients from Ethiopia, Expression of Anti-Inflammatory Cytokines was Greater than that of Proinflammatory Cytokines

Abstract

The immunopathology of cutaneous leishmaniasis (CL) caused by Leishmania aethopica is not well understood. This study aimed to characterize the host's localized immune response in formalin-fixed paraffin-embedded (FFPE) skin biopsies taken from skin lesions of patients who had developed localized CL due to infection with L. aethiopica. A retrospective cross-sectional study was conducted on 40 FFPE skin biopsy samples collected from 2018 to 2022 in the ALERT hospital, Addis Ababa, Ethiopia. Immunohistochemical techniques were used to examine localized immune T helper 1 (Th1) and T helper 2 (Th2) cytokines. GraphPad Prism v. 10 was used for statistical analysis and visualization. The Mann-Whitney U test and Kruskal-Wallis tests were used to compare the median values of different groups of cytokines and cell markers. In comparison with healthy controls (n = 11), localized CL patients (n = 40) had higher expression levels of anti-inflammatory Th2 cytokines (IL-10 and TGF-β) (P <0.0001) than proinflammatory cytokines (IFNγ and TNF-α). Further, when comparing localized CL patients with healthy controls, the median value of CD8 marker expression was slightly higher than that of CD4 marker expression, although not statistically significant. Our immunohistochemical analysis indicates that in the skin lesions of patients with localized CL, L. aethiopica infection is associated with greater local availability of Th2-associated anti-inflammatory cytokines in comparison with Th1-associated proinflammatory cytokines. The current study offers a paradigm for researching local cytokine production in parasitic infection and supports findings linking unique cytokine expression profiles to the immunopathogenesis of human CL.