Abstract
Introduction: Leprosy is an infectious disease caused by Mycobacterium leprae, a debilitating disease that affects the skin and peripheral nerves. It is possible that tissue changes during infection with leprosy are related to alterations in the activity of the Notch signaling pathway, an innate signaling pathway in the physiology of the skin and peripheral nerves.Methods: This is a descriptive observational study. Thirty skin biopsies from leprosy patients and 15 from individuals with no history of this disease were evaluated. In these samples, gene expressions of cellular components associated with the Notch signaling pathway, Hes-1, Hey-1, Runx-1 Jagged-1, Notch-1, and Numb, were evaluated using q-PCR, and protein expression was evaluated using immunohistochemistry of Runx-1 and Hes-1.Results: Changes were observed in the transcription of Notch signaling pathway components; Hes-1 was downregulated and Runx-1 upregulated in the skin of infected patients. These results were confirmed by immunohistochemistry, where reduction of Hes-1 expression was found in the epidermis, eccrine glands, and hair follicles. Increased expression of Runx-1 was found in inflammatory cells in the dermis of infected patients; however, it is not related to tissue changes. With these results, a multivariate analysis was performed to determine the causes of transcription factor Hes-1 reduction. It was concluded that tissue inflammation was the main cause.Conclusions: The tissue changes found in the skin of infected patients could be associated with a reduction in the expression of Hes-1, a situation that would promote the survival and proliferation of M. leprae in this tissue.
Highlights
Leprosy is an infectious disease caused by Mycobacterium leprae, a debilitating disease that affects the skin and peripheral nerves
When evaluating the transcription of genes related to the Notch signaling pathway, we found significant changes in the expression of Hes-1 and Runx-1 in leprosy samples, Hes-1 gene was found to be downregulated in the samples of leprosy patients This allows us to infer that Hes-1 would not be related to the deterioration of the dermal nerve fiber caused by M. leprae, given that Hes-1 overexpression is necessary to induce nerve damage [10]
On the other hand, based on the inflammatory mechanism explaining the reduction of Hes-1, we ask the question: why was the transcriptional factor Runx-1 not altered in leprosy patients, considering that some Notch transcription factors are affected in inflammatory environments? The answer we suggest is that Runx-1 can be expressed through two pathways, one that is given by the interaction of Jagged ligands with the Notch-1 receptor and a second that is mediated by the union of Deltatype ligands with this receptor [43]; it has been demonstrated that this interaction (Delta-Notch) is not involved in inflammatory processes [41], which confirms our findings
Summary
Leprosy is an infectious disease caused by Mycobacterium leprae, a debilitating disease that affects the skin and peripheral nerves. Leprosy is a neglected infectious disease caused by Mycobacterium leprae, an obligate intracellular microorganism that cannot be cultivated in axenic media [1] This mycobacterium is characterized by a marked affinity for the skin and peripheral nerve trunks and is responsible for the disability of more than four million people worldwide [2]. One measure that in the future could have an impact on reducing the burden and disability generated by M. leprae is to deepen our understanding of the physiopathogenic mechanisms related to disability and the proliferation of this mycobacterium in the host, from which tools can be generated to facilitate its detection and control One of these mechanisms could be related to changes in the activation of the Notch signaling pathway, which is an innate cellular component involved in multiple processes of cellular proliferation and differentiation at the levels of the skin and peripheral nerves [6, 7]
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