Elsevier

Microbial Pathogenesis

Volume 91, February 2016, Pages 18-25
Microbial Pathogenesis

Langerhans cells (CD1a and CD207), dermal dendrocytes (FXIIIa) and plasmacytoid dendritic cells (CD123) in skin lesions of leprosy patients

https://doi.org/10.1016/j.micpath.2015.11.013Get rights and content

Highlights

  • Mycobacterium leprae infections varies widely and depends on the pattern of the host immune response.

  • Dendritic cells play an important role in the activation of the innate and adaptive immune system.

  • The analysis of dendritic cells was done by immunohistochemistry.

  • Results indicate the existence of a larger number of dendritic cells in tuberculoid leprosy.

  • Dendritic cells favoring an efficient immune response to M. leprae.

Abstract

The clinical course of infection with Mycobacterium leprae varies widely and depends on the pattern of the host immune response. Dendritic cells play an important role in the activation of the innate and adaptive immune system and seem to be essential for the development of the disease. To analyze the presence of epidermal dendritic cells (CD1a and CD207), plasmacytoid dendritic cells (CD123) and dermal dendrocytes (factor XIIIa) in lesion fragments of leprosy patients, skin samples from 30 patients were studied. These samples were submitted to immunohistochemistry against CD1a, CD207, FXIIIa, and CD123. The results showed a larger number of Langerhans cells, detected with the CD1a or CD207 marker, dermal dendrocytes and plasmacytoid dendritic cells in patients with the tuberculoid form. A positive correlation was observed between the Langerhans cell markers CD1a and CD207 in both the tuberculoid and lepromatous forms, and between Langerhans cells and dermal dendrocytes in samples with the tuberculoid form. The present results indicate the existence of a larger number of dendritic cells in patients at the resistant pole of the disease (tuberculoid) and suggest that the different dendritic cells studied play a role, favoring an efficient immune response against infection with M. leprae.

Introduction

Leprosy is a chronic disease caused by the obligate intracellular bacillus Mycobacterium leprae, which mainly affects the skin and peripheral nerves. The diagnosis and treatment of leprosy are well established in the literature. However, a late diagnosis and treatment can have severe consequences for patients and their contacts due to the great disabling potential of the disease [1], [2], [3], [4], [5].

M. leprae is able to infect a large number of individuals; however, few infected individuals become sick because of the low pathogenicity of the microorganism, a property that is not only due to the intrinsic characteristics of the bacillus, but depends primarily on its relationship with the host and the degree of endemicity of the environment. Active infection with M. leprae shows a broad clinical spectrum, ranging from paucibacillary disease characterized by the presence of few bacilli to multibacillary disease characterized by a high bacillary load in the lesions [6], [7].

The clinical manifestations of leprosy are highly variable and are determined by the host's immune response against the bacillus [8], [9], [10]. Depending on the cytokines secreted during infection, T lymphocytes induce the development of milder disease or even cure [11] through a cell-mediated (Th1 type) response, or a response that is not as effective against the bacillus, called humoral or Th2 response [12], [13].

The Th1 subpopulation produces IL-2 and IFN-γ, cytokines that are responsible for the maintenance of the cell-mediated immune response. IL-2 activates CD4+ lymphocyte receptors and induces natural killer cells to produce IFN-γ which, in turn, acts on macrophages to stimulate phagocytosis [8]. The Th2 subpopulation produces immunosuppressive cytokines such as IL-4 and IL-10, which suppress macrophage activity and stimulates B lymphocytes to differentiate into plasma cells which produce immunoglobulins [8].

Dendritic cells play an important role in the activation of the innate and adaptive immune system and seem to be essential for the development of leprosy, since these cells are specialized in the processing and presentation of antigens, a function that can influence the outcome of infection [14].

Langerhans cells in the steady-state are immature, highly endocytic and form a dense network in the epidermis where they constantly screen the environment for invading antigens. These cells are ideally positioned to detect any pathogen that breaks the skin barrier [15], [16], [17]. Langerhans cells express the CD1a molecule, which presents lipid antigens to T cells, and CD207 (langerin), a C-type lectin that induces the formation of Birbeck granules, a specific endosomal structure of Langerhans cells [18], [19].

Dermal dendrocytes are found in the normal dermis where they predominate in the papillary dermis and in the perivascular adventitial layer. However, an increase in these cells is observed in inflammatory and neoplastic diseases. Dermal dendrocytes serve as a tissue reserve of factor XIIIa (FXIIIa) which is important for tissue healing [20], and act together with mast cells in processes of extracellular matrix remodeling [21].

Rarely observed in normal skin, plasmacytoid dendritic cells (pDCs) have a morphology that resembles plasma cells. These cells are abundantly found in lymphoid organs and in blood, and are rapidly recruited to the target site of bacterial or viral infection or inflammation [22], [23], [24]. pDCs express the CD123 molecule, the alpha chain of the IL-3 receptor. This marker is expressed at high levels on the surface of these cells since they require IL-3 for their differentiation [25]. pDCs express high levels of TLR7 and TLR9 which are expressed in the endoplasmic reticulum and endosomal membranes. They detect intracellular microbial nucleic acid [22], [23], [24], [25].

So far few studies have investigated the concomitant expression of all these markers in skin lesions of patients with leprosy. The objective of the present study was to analyze by immunohistochemistry the presence of epidermal dendritic cells (CD1a and CD207), pDCs (CD123) and dermal dendrocytes (FXIIIa) in skin lesion fragments of leprosy patients, and to associate the presence of these cells with the polar forms of the disease.

Section snippets

Sample

Thirty paraffin blocks of skin fragments from untreated patients with a diagnosis of leprosy, 16 with the tuberculoid form and 14 with the lepromatous form, collected at partner institutions of the Laboratory of Immunopathology, Center of Tropical Medicine, Federal University of Para, were used. The diagnosis was made by dermatoneurological and histopathological analysis and identification of bacilli in the samples according to the classification of Ridley-Jopling [26].

Immunohistochemistry

The samples were obtained

Langerhans cells

The use of the langerin (CD207) and CD1a markers revealed the presence of Langerhans cells in the epidermis. These cells had an irregular appearance, and long and thin cytoplasmic prolongations (Fig. 1A and B).

Quantitative analysis of CD1a immunostaining showed a significantly (p = 0.0209) larger median number in patients with tuberculoid leprosy (0.6094 ± 0.416 cells/field) compared to those with the lepromatous form (0.2750 ± 0.4164 cells/field) (Fig. 4A). The median number of CD207-positive

Discussion

The results of this study showed a significant difference in CD1a and langerin immunostaining between the different poles of leprosy. The number of CD1a stained cells in the epidermis was higher in patients with the tuberculoid form (0.6094 cells/field) compared to lepromatous patients (0.2750 cells/field). Immunostaining for langerin (CD207) was significantly higher (p = 0.0373) in patients with tuberculoid leprosy (1.569 cells/field) compared to patients at the lepromatous pole

Disclosure

The authors declare no conflict of interest.

Acknowledgments

This project has been funded in whole or in part with funds from the Conselho Nacional de Pesquisa – CNPq – Brazil, grants 402738/2005-5 and 401223/2005-1.

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