Abstract
Mycobacterium leprae causes leprosy, a dermatoneurological disease which affects the skin and peripheral nerves. One of several cellular structures affected during M. leprae infection is the endoplasmic reticulum (ER). Infection by microorganisms can result in ER stress and lead to the accumulation of unfolded or poorly folded proteins. To restore homeostasis in the cell, the cell induces a series of signaling cascades known as the unfolded protein response called UPR (unfolded protein response). The present work is aimed at investigating the in situ expression of these markers in cutaneous lesions of clinical forms of leprosy and establish possible correlation expression patterns and types of lesion. A total of 43 samples from leprosy patients were analyzed by immunohistochemistry with monoclonal antibodies against GRP78/BiP, PERK, IRE1α, and ATF6. A statistically significant difference between the indeterminate, tuberculoid, and lepromatous clinical forms was detected, with high expression of GRP78/BiP, PERK, IRE1α, and ATF6 in tuberculoid forms (TT) when compared to lepromatous leprosy (LL) and indeterminate (I) leprosy. These results represent the first evidence of ER stress in samples of skin lesions from leprosy patients. We believe that they will provide better understanding of the complex pathogenesis of the disease and facilitate further characterization of the cascade of molecular events elicited during infection.
Highlights
Leprosy is the clinical manifestation of a dermatoneurological disease caused by infection with Mycobacterium leprae
The histopathological characteristics of the lesions were visible in the I focal lymphohistiocytic inflammatory infiltrate distributed around appendages, nervous fillets, and vessels; sometimes, they were positive by bacilloscopy
Such extension of the infiltrate might compromise the deep dermis until the hypodermis, preventing macrophages from eliminating the bacilli and allowing them instead to accumulate in the cytoplasm, sometimes in globies as demonstrated by Ziehl-Neelsen staining (Figure 1)
Summary
Leprosy is the clinical manifestation of a dermatoneurological disease caused by infection with Mycobacterium leprae. The interaction between M. leprae and the host is complex, and the disease presents a chronic evolution that affects mainly the skin and peripheral nerves. Its clinical manifestations vary and are associated with diverse host-dependent factors such as the pattern of innate and adaptive immune response, as well as genetic and immunogenetic factors [1,2,3]. Immune response patterns to M. leprae have been shown to involve components of innate immunity, such as dendritic cells, macrophages (both M1 and M2 subtypes), and natural killer cells, as well as diverse types of lymphocytes, such as T helper cells (Th1, Th2, Th17, Th9, Th22, and Th25) [4,5,6,7,8]. In situ techniques have revealed alterations in several cellular structures and signaling pathways in the skin during such response. One of them is the endoplasmic reticulum (ER), which is involved in the Disease Markers biosynthesis of lipids and proteins, as well as intracellular signaling, and is, essential for the proper functioning of the cell [12,13,14]
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