Abstract

Leprosy is a chronic disease caused by Mycobacterium leprae that affects the skin and peripheral nerves. It may present as one of two distinct poles: the self-limiting tuberculoid leprosy and the highly infectious lepromatous leprosy (LL) characterized by M. leprae-specific absence of cellular immune response. The pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) enhance the bactericide activities of macrophages after interaction with its receptor, CD74. Importantly, MIF also possesses chemoattractant properties, and it is a key factor in situ for the activation of macrophages and in blood to promote leukocytes migration. MIF-mediated activation of macrophages is a key process for the elimination of pathogens such as Mycobacterium tuberculosis; however, its participation for the clearance of M. leprae is unclear. The aim of this study was to evaluate the serum levels of MIF as well as MIF and CD74 expression in skin lesions of LL and compare it with healthy skin (HSk) taken from subjects attending to dermatological consult. Samples of serum and skin biopsies were taken from 39 LL patients and compared with 36 serum samples of healthy subjects (HS) and 10 biopsies of HSk. Serum samples were analyzed by ELISA and skin biopsies by immunohistochemistry (IHC). IHC smears were observed in 12 100× microscopic fields, in which percentage of stained cells and staining intensity were evaluated. Both variables were used to calculate a semi-quantitative expression score that ranged from 0 to 3+. We found no differences in MIF levels between LL patients and HS in sera. In addition, MIF was observed in over 75% of cells with high intensity in the skin of patients and HSk. Although we found no differences in MIF expression between the groups, a CD74 score statistically higher was found in LL skin than HSk (p < 0.001); this was the result of a higher percentage of cells positive for CD74 (p < 0.001). As a conclusion, we found that CD74-positive cells are intensely recruited to the skin with LL lesions. In this manner, MIF signaling may be enhanced in the skin of LL patients due to increased expression of its receptor, but further studies are required.

Highlights

  • Leprosy is a chronic infectious disease caused by Mycobacterium leprae

  • We analyzed the expression of migration inhibition factor (MIF) and CD74 in skin biopsies of 39 lepromatous leprosy (LL) patients as well as 10 samples of healthy skin (HSk)

  • We found that most of the LL skin samples could be classified as 1+ (37.2%) or 2+ (34.9%); most of HSk fell into 1+ (30%) and 2+ (40%) categories

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Summary

Introduction

The disease in patients may develop as one of two poles that differ clinically and immunologically between each other. Few lesions in the body and an active immune response mediated by cells characterize the tuberculoid leprosy (TT) pole; on the other hand, patients who develop lepromatous leprosy (LL) show numerous erythematous macules around the body coupled with M. leprae-specific anergy and disrupted immune response. As a consequence of the immunological imbalance, macrophages get infested by abundant bacilli and become foamy macrophages [4]. These macrophages seem unable to kill M. leprae but serve as a reservoir instead and release additional anti-inflammatory mediators and reduce their production of key activator cytokines, namely TNF-α and IL-1β [5]

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