Cutaneous Leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the Leishmania genus. The disease manifests with diverse clinical presentations, ranging from self-healing cutaneous lesions to disfiguring mucocutaneous forms. The systemic immune response plays a pivotal role in the pathogenesis of CL, orchestrating a complex interplay between host defense mechanisms and parasite evasion strategies. This review provides a comprehensive overview of the systemic immune response in the context of CL pathogenesis, highlighting key immunological factors implicated in disease progression and outcome. Through a synthesis of current literature, this review elucidates the dynamic interactions between innate and adaptive immune components, cytokine networks and immune evasion mechanisms employed by Leishmania parasites. Insights gained from understanding the systemic immune response in CL not only contribute to our knowledge of parasitehost interactions but also offer potential avenues for the development of immunotherapeutic strategies and vaccines.
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