02351nas a2200253   4500000000100000008004100001653002300042653002400065653001800089653002800107653002500135653002500160653001200185653002300197653001300220100001900233700002000252700002100272245008500293300001200378490000800390520168600398022001302084       2017                            d10aVitamin D receptor10aToll-Like Receptors10aT lymphocytes10aNotch signaling pathway10aNatural killer cells10aMycobacterium leprae10aleprosy10aImmunopathogenesis10aImmunity1 aSerrano-Coll H1 aAcevedo-Saenz L1 aCardona-Castro N00aA hypothetical role for Notch signaling pathway in immunopathogenesis of leprosy  a162-1690 v1093 a<p>Leprosy is a chronic infectious disease caused by <em>Mycobacterium leprae</em> 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 <em>M. leprae</em> 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.</p>
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