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Endoplasmic Reticulum Stress Markers and Their Possible Implications in Leprosy's Pathogenesis
Kelly Emi Hirai1, Jorge Rodrigues de Sousa2,3, Luciana Mota Silva1
1Center of Biological and Health Sciences, State University of Pará, Belém, PA, Brazil.
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.
Insights
Leprosy infection triggers endoplasmic reticulum (ER) stress, activating the unfolded protein response (UPR). This study found higher UPR marker expression in tuberculoid leprosy skin lesions compared to lepromatous forms.
Area of Science:
- Cellular biology
- Immunology
- Pathogenesis of infectious diseases
Background:
- Leprosy, caused by *Mycobacterium leprae*, is a dermatoneurological disease impacting skin and nerves.
- Microbial infections can induce endoplasmic reticulum (ER) stress, leading to unfolded protein accumulation.
- The unfolded protein response (UPR) is a cellular mechanism to restore homeostasis during ER stress.
Purpose of the Study:
- To investigate the in situ expression of UPR markers in leprosy skin lesions.
- To correlate UPR expression patterns with different clinical forms of leprosy.
Main Methods:
- Immunohistochemistry was used to analyze 43 leprosy patient skin lesion samples.
- Monoclonal antibodies against GRP78/BiP, PERK, IRE1α, and ATF6 were employed.
- Expression levels were compared across indeterminate, tuberculoid, and lepromatous leprosy forms.
Main Results:
- A statistically significant difference in UPR marker expression was observed among leprosy clinical forms.
- Tuberculoid leprosy (TT) showed significantly higher expression of GRP78/BiP, PERK, IRE1α, and ATF6 compared to lepromatous (LL) and indeterminate (I) forms.
- This study provides the first evidence of ER stress in leprosy skin lesions.
Conclusions:
- The findings demonstrate ER stress and UPR activation in leprosy skin lesions.
- Differential UPR marker expression correlates with distinct clinical forms of leprosy.
- This research enhances understanding of leprosy pathogenesis and associated molecular events.