A hypothetical role for Notch signaling pathway in immunopathogenesis of leprosy

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TitleA hypothetical role for Notch signaling pathway in immunopathogenesis of leprosy
Publication TypeJournal Article
AuthorsSerrano-Coll H, Acevedo-Saenz L, Cardona-Castro N
Abbrev. JournalMed. Hypotheses
JournalMedical hypotheses
Year of Publication2017
Publication Languageeng
KeywordsImmunity, Immunopathogenesis, Leprosy, Mycobacterium leprae, Natural killer cells, Notch signaling pathway, T lymphocytes, Toll-Like Receptors, Vitamin D receptor

Leprosy is a chronic infectious disease caused by Mycobacterium leprae mainly affecting skin and peripheral nerves. Leprosy has a broad range of clinical manifestations that range from mild (tuberculoid leprosy) to severe (lepromatous leprosy) forms, and are highly dependent on the host’s immune response. Among the immune response elements involved in the pathogenesis of leprosy are the Toll-like receptors (TLRs), vitamin D receptor (VDR), natural killer cells (NK), and T cells. These innate and adaptive immune response elements may be related to the Notch signaling pathway, which is involved in immune cell growth, differentiation, and proliferation. We hypothesize that failure in Notch signaling in leprosy patients may be associated to: 1) compromising NK cell maturation, lysing of infected cells, and CD4+ Th1 differentiation. 2) VDR alterations and TLR polymorphisms may affect expression of Notch Delta-like ligands (DLL) in antigen presenting cells (APCs). 3) altered DLL expression by APCs could compromise CD4+ T cell differentiation towards the Th1 and Th17 effector phenotypes; and finally 4) expression of Notch Jagged ligands would induce CD4+ T cell differentiation towards Th2 effector phenotype and alternative activation of macrophages. Altogether, these signaling failures could favor proliferation of M. leprae in the host. Therefore, evidence of the proposed immunologic failures in leprosy patients would be essential for the better understanding of immunopathogenesis of this disease, and would ultimately enable detection of susceptible individuals, providing a valuable tool for prevention of this debilitating disease.