Immuno-Informatics Insight into Relationship Between Cholesterol and Cytokines in Cutaneous Leishmaniasis

Objectives: The role of serum cholesterol and its interactions with cytokines in the pathophysiology of human cutaneous leishmaniasis (CL) is not known. This study was aimed to evaluate the correlation between serum total cholesterol (TC), very-low-density lipoprotein-cholesterol (VLDL-C), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG), and cytokines including interleukin-10 (IL10), interleukin-12 (IL12), tumor necrosis factor-alpha (TNF-α), in CL. Moreover, we analyzed the cholesterol-cytokine network to shed light on the pathogenesis of CL. Methods: A case-control study including CL patients (n = 50) and control subjects (n = 25) ranging between 20-30 years old was conducted from December 2022 to March 2023. The serum samples were analyzed via commercial kits to detect the levels of TC, IL-10, IL-12, TNF-α, VLDL-C, LDL-C, HDL-C and TG. Computational efforts to dissect cholesterol-protein interaction networks was also employed using STITCH. Results: TC, HDL-C, and LDL-C levels were markedly lower (p =0.0001) in CL patients compared to those of control subjects, whereas IL10, IL12, TNF-α, VLDL-C and TG levels were higher in CL patients. Serum cholesterol did not exhibit a correlation with cytokines, however a significant correlation (r = 0.57; p = 0.026) was observed between IL12 and TNF-α. Within the cholesterol-protein network, cholesterol potentially interacted with IL10, connecting cholesterol to modules with immunological significance, including TARAF1, TARAF2, and TNFRSF1B, as well as IL10, IL10RA, and IL12RB1. Conclusion: This study showed alteration of lipid and lipoprotein in CL, and it introduced two immunological modules in CL which appreciates attention to the altered cholesterol-cytokine interaction network in CL.