Endoplasmic Reticulum Stress Markers and Their Possible Implications in Leprosy’s Pathogenesis

CNPq/Brazil (Grant numbers 302553/2015-0 and 116427/2016-7) State University of Par?. Center of Biological and Health Sciences. Bel?m, PA, Brazil. Federal University of Par?. Tropical Medicine Center. Bel?m, PA, Brazil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. State University of Par?. Center of Biological and Health Sciences. Bel?m, PA, Brazil. State University of Par?. Center of Biological and Health Sciences. Bel?m, PA, Brazil. State University of Par?. Center of Biological and Health Sciences. Bel?m, PA, Brazil. State University of Par?. Center of Biological and Health Sciences. Bel?m, PA, Brazil. S?o Paulo University. School of Medicine. S?o Paulo, SP, Brazil / S?o Paulo University. Tropical Medicine Institute. S?o Paulo, SP, Brazil. State University of Par?. Center of Biological and Health Sciences. Bel?m, PA, Brazil / Federal University of Par?. Tropical Medicine Center. Bel?m, PA, Brazil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / S?o Paulo University. Tropical Medicine Institute. S?o Paulo, SP, Brazil. State University of Par?. Center of Biological and Health Sciences. Bel?m, PA, Brazil. 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, IRE1?, and ATF6. A statistically significant difference between the indeterminate, tuberculoid, and lepromatous clinical forms was detected, with high expression of GRP78/BiP, PERK, IRE1?, 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.