Modern aspects of leprosy immunopathogenesis: from classical paradigms to novel therapeutic approaches

Modern research demonstrates that the immunopathogenesis of leprosy is not limited to the classical Th1/Th2 dichotomy, but involves a much broader spectrum of cellular and molecular interactions. Aim. To systematize current concepts of the complex immunopathogenetic mechanisms of leprosy that extend beyond the classical Th1/Th2 dichotomy and to consider potential immunotherapeutic strategies. Materials and methods. An analysis of contemporary Russian and international scientific publications on the immunology of leprosy was conducted using PubMed, Scopus, and eLibrary databases. Results. The immune response in leprosy is a dynamic network where the balance between effector lymphocyte populations (Th1, Th17) and regulatory cells (Treg, M2 macrophages), as well as the functional state of dendritic cells and innate lymphoid cells, plays a critical role. Mycobacterium leprae possesses a wide array of immune evasion mechanisms, including suppression of antigen presentation, induction of an immunosuppressive microenvironment, and metabolic reprogramming of host cells. Leprosy reactions (type 1 and type 2) result from an acute disruption of this balance and are characterized by cytokine dysregulation. Conclusion. Understanding the expanded immunoregulatory network in leprosy opens prospects for developing adjunctive therapies, such as targeted cytokine therapy, Treg-directed immunomodulation, and interventions that correct macrophage metabolism. These approaches aim to modulate the immune response, which is particularly relevant for the treatment of severe and reactive forms of the disease.

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