Tinara Leila de Souza Aarão

In situ expression of M2 macrophage subpopulation in leprosy skin lesions

The clinical manifestations of the leprosy depend on host immune response and the macrophages are the primary cells involved in this process. M1 and M2 cells exhibited distinct morphology, distinct surface marker profiles, as well as different cytokine and chemokine secretion. Macrophages express receptors such as CD163, CD68, CD206, and costimulatory molecules such as CD80 and CD86, and cytokines that trigger a suppressive or inflammatory response. Thirty-three untreated patients were selected, 17 patients had the tuberculoid leprosy (TT) and 16 had the lepromatous leprosy (LL). We performed immunohistochemistry to detect IL-13, IL-10, TGF-β, FGF-β, CD163, CD68, arginase 1. M2 macrophages showed significant differences between the groups studied with increase in the expression of costimulatory molecules (CD68 and CD163), arginase 1 and cytokines (IL-10, IL-13, TGF-β and FGF-b) in the LL form. Response of M2 macrophages emerge as an alternative for a better understanding of the innate immunity in the polar forms of leprosy, highlighting the role of cytokines, arginase 1 and costimulatory molecules in the repair and suppressive responses in the lepromatous form of the disease.

Th9 cytokines response and its possible implications in the immunopathogenesis of leprosy

Aims Leprosy is an infectious-contagious disease whose clinical evolution depends on the interaction of the infectious agent with the immune response of the host, leading to a clinical spectrum that ranges from lepromatous leprosy (susceptibility, LL) to tuberculoid leprosy (resistance, TT). The immune response profile will depend on the pattern of cytokine production and on the activity of macrophages during infection. Classically, the clinical evolution of leprosy has been associated with Th1/Th2 cytokine profiles, but the role of new cytokine profiles such as T helper 9 (Th9) remains to be elucidated. Methods To evaluate the tissue expression profile of these cytokines, a cross-sectional study was conducted using a sample of 30 leprosy skin lesion biopsies obtained from patients with leprosy, 16 TT and 14 lepromatous LL. Results Immunohistochemical analysis revealed a significant difference in interleukin (IL)-9, IL-4 transforming growth factor (TGF)-β and IL-10 levels between the two groups. IL-9 was more expressed in TT lesions compared with LL lesions. Higher expression of IL-4, IL-10 and TGF-β was observed in LL compared with TT. IL-4, IL-10 and TGF-β tended to be negatively correlated with the expression of IL-9, indicating a possible antagonistic activity in tissue. Conclusions The results suggest that Th9 lymphocytes may be involved in the response to Mycobacterium leprae, positively or negatively regulating microbicidal activity of the local immune system in the disease.

Immunohistochemical analysis of the expression of cellular transcription NFκB (p65), AP-1 (c-Fos and c-Jun), and JAK/STAT in leprosy ☆ ☆☆

Leprosy is a disease whose clinical spectrum depends on the cytokine patterns produced during the early stages of the immune response. The main objective of this study was to describe the activation pattern of cellular transcription factors and to correlate these factors with the clinical forms of leprosy. Skin samples were obtained from 16 patients with the tuberculoid (TT) form and 14 with the lepromatous (LL) form. The histologic sections were immunostained with anti-c-Fos and anti-c-Jun monoclonal antibodies for investigation of AP-1, anti-NFκB p65 for the study of NFκB, and anti-JAK2, STAT1, STAT3, and STAT4 for investigation of the JAK/STAT pathway. Cells expressing STAT1 were more frequent in the TT form than in LL lesions (P = .0096), in agreement with the protective immunity provided by IFN-γ. STAT4 was also more highly expressed in the TT form than in the LL form (P = .0098). This transcription factor is essential for the development of a Th1 response because it is associated with interleukin-12. NFκB (p65) and STAT4 expression in the TT form showed a strong and significant correlation (r = 0.7556 and P = .0007). A moderate and significant correlation was observed between JAK2 and STAT4 in the TT form (r = 0.6637 and P = .0051), with these factors responding to interleukin-12 in Th1 profiles. The results suggest that STAT1, JAK2, and NFκB, together with STAT4, contribute to the development of cell-mediated immunity, which is able to contain the proliferation of Mycobacterium leprae.

Relationship between growth factors and its implication in the pathogenesis of leprosy.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae which affects the skin and peripheral nervous system. The immune response of the host determines the clinical course of the disease. The tuberculoid form is the result of high cell-mediated immunity characterized by a Th1 response, whereas the lepromatous form is characterized by low cell-mediated immunity and a Th2 humoral response. The neural damage established produces marked changes in the expression of growth factors such as nerve growth factor (NGF) and its receptors (NGF-R). The expression of NGF, associated with the expression of Th1 and Th2 cytokines, might be involved in the tissue damage caused by the bacillus. Therefore, the objective of this study was to correlate the immunoexpression patterns of NGF and NGF-R in the different clinical forms of leprosy, and to associate the findings with the in situ expression of TGF-β and clinical classification of the disease. TGF-β, NGF and NGF-R immunoexpression was analyzed by immunohistochemistry in paraffin-embedded material. Most patients were males with a mean age of 40.7 years. TGF-β levels were significantly higher in the lepromatous forms. No significant difference in the immunoexpression of NGF or NGF-R was observed between the clinical forms, but expression tended to be higher at the lepromatous pole. There was a significant positive correlation between NGF and NGF-R in the different clinical forms of leprosy. A significant positive correlation was observed between NGF, NGF-R and TGF-β. It can be concluded that, even existing evidence on the role of these molecules in the clinical spectrum of leprosy.

E-selectin and P-selectin expression in endothelium of leprosy skin lesions.

Leprosy is an infectious-contagious disease whose clinical evolution depends on the immune response pattern of the host. Adhesion molecules and leukocyte migration from blood to tissue are of the utmost importance for the recognition and elimination of infectious pathogens. Selectins are transmembrane glycoproteins that share a similar structural organization and can be divided into three types according to their site of expression. The biopsies were cut into 5μm thick sections and submitted to immunohistochemistry using antibodies against E-selectin and P-selectin. The number of E-selectin-positive cells was significantly higher in the tuberculoid form than in the lepromatous form. The immunostaining pattern of P-selectin differed from that of E-selectin. Analysis showed a larger number of endothelial cells expressing CD62P in the lepromatous form compared to the tuberculoid form. The presence of these adhesins in the endothelium contributing to or impairing the recruitment of immune cells to inflamed tissue and consequently influences the pattern of immune response and the clinical presentation of the disease.

Immunohistochemical analysis of the expression of TNF-alpha, TGF-beta, and caspase-3 in subcutaneous tissue of patients with HIV Lipodystrophy Syndrome

INTRODUCTION HIV Lipodystrophy Syndrome (HIVLS) is a multifactorial clinical expression that presents alterations in the metabolism and distribution pattern of body fat via immunological changes capable of disrupting homeostasis. This study aimed to analyze the degree of inflammatory, anti-inflammatory, and apoptosis activity in the subcutaneous tissue of patients, based on the expression of Tumor Necrosis Factor-α (TNF-α), Transforming Growth Factor-β (TGF-β), and caspase-3, respectively, and correlate them with clinical data and with each other. METHODS This is a cross-analytical study. The biopsy of subcutaneous cellular tissue was performed on the right thigh of 19 patients with HIVLS who were attended to at a university hospital, and four people without HIV and lipodystrophy, for comparison. The type of lipodystrophy and the estimation of body fat were obtained during the consultation or obtained from medical charts. The cytokine expression was observed in the adipose tissue through the streptavidin-biotin peroxidase method, and analyzed by optical microscopy. RESULTS Despite the mixed clinical form having been prevalent in both genders, men were more lipoatrophic and women were more lipohypertrophic. Men showed higher expression of TNF-α and caspase-3 than women. Patients with lipodystrophy had higher expression of TNF-α and caspase-3 and lower TGF-β, compared to the control group. The percentage of body fat was negatively correlated with the expression of TNF-α and caspase-3. Longer durations of infection and use of antiretroviral therapy (ARVT) were positively associated with the levels of TNF-α. The expression of caspase-3 and TGF-β was associated with higher levels of TNF-α. CONCLUSION Regardless of the clinical form, HIVLS is characterized by a chronic inflammatory process associated with the male gender, the percentage of body fat, and lipoatrophy manifestations. There is increased apoptotic activity in more inflamed tissues and there is correlation between TNF-α and TGF-β, which suggests a possible negative feedback mechanism between the inflammatory and anti-inflammatory activity.

Response of iNOS and its relationship with IL-22 and STAT3 in macrophage activity in the polar forms of leprosy

Leprosy is a chronic granulomatous infection that manifests as different clinical forms related to the immunological response. The aim of the study was to evaluated the response of IL-22, STAT3, CD68 and iNOS in leprosy skin lesions. The mean number IL-22 positive cells was 12.12±1.90cells/field in the TT form and 31.31±2.91cells/field in the LL form. STAT3 positive cells was 5.29±1.96 cells/field in the TT form, while this number was 11.13±3.48cells/field in the LL form. The mean number of CD68 positive cells was 25.18±6.21cells/field in the TT form and 62.81±8.13cells/field in the LL form. Quantitative analysis of iNOS revealed a significant difference, with the mean number of cells expressing the enzyme being 30.24±2.88cells/field in the TT form compared to 35.44±4.69cells/field in the LL form. Linear correlations in lesions of TT patients showed a moderate positive correlations between CD68 and iNOS, STAT3 and Inos, IL-22 and STAT3, and IL-22 and iNOS. Our results demonstrate that these factors can act synergistically to induce a microbicidal activity in the population of macrophages in the leprosy lesions.

Environmental impact and seroepidemiology of HTLV in two communities in the eastern Brazilian amazon.

The objective of this study was to detect antibodies for human T lymphotropic virus (HTLV) in subjects residing in two communities located in the eastern Brazilian Amazon and on the shores of the Tucuruí hydroelectric power plant. A total of 657 serum samples were analysed using an enzyme‐linked immunosorbent assay with an anti‐HTLV antibody (Symbiosis™, São Paulo, Brazil), demonstrating a virus prevalence of 4.7%. Most individuals with HTLV were aged over 30 years (P = 0.013), were unmarried (P = 0.019), resided in the area for more than 10 years (P = 0.001), had a low level of education (P = 0.015), and had a family income of up to

Imunorreatividade das células dendríticas nas lesões foveolares da hanseníase dimorfa

305 (100%). In contrast, there was no significant association between infection and sex, city of birth, haemotransfusion, or previous surgery. The prevalence observed in these communities suggests that the residents should be concerned about HTLV infection, and that some areas may become endemic for HTLV. J. Med. Virol. 85:1585–1590, 2013.

Inmunoexpresión de TNF-α y TGF-β en lesiones de pacientes en las diversas formas clínicas de la hanseniasis a través de técnica de inmunohistoquímica

Leprosy is an infectious and contagious disease, whose etiologic agent is the Mycobacterium leprae, mainly characterized by neural and dermatologic injures. The tuberculoid and lepromatous leprosy types are called polar and considered stable forms. Between them there is the borderline group that shows immunologic instability with variable clinical forms, and it presents a lesion with infiltred border and center of healthy skin, called foveolar lesion. This study aimed to analyze the immunoreactivity of dendritic cells in the apparently healthy skin inside the central region and the infiltred edge of the foveolar lesion in borderline leprosy. It is an analytical and transversal study. CD1a and FXIIIa markers were used to count the dendritic cells in skin samples. A predominance of CD1a and FXIIIa cells in the foveolar border lesion was observed as compared to the center area of the lesion. The prevalence of dendritic cells at the edge of the foveolar lesion can be justified by the pattern of inflammatory and immune response to M. leprae. The distribution of M. leprae may be concentrated in this region, promoting a greater antigenic exposure. The comparison between the center and the edge of the foveolar lesion has obtained a quantitative difference indicating a basic function of dendritic cells in response to M. leprae and, consequently, in the course of the disease.Leprosy is an infectious and contagious disease, whose etiologic agent is the Mycobacterium leprae, mainly characterized by neural and dermatologic injures. The tuberculoid and lepromatous leprosy types are called polar and considered stable forms. Between them there is the borderline group that shows immunologic instability with variable clinical forms, and it presents a lesion with infiltred border and center of healthy skin, called foveolar lesion. This study aimed to analyze the immunoreactivity of dendritic cells in the apparently healthy skin inside the central region and the infiltred edge of the foveolar lesion in borderline leprosy. It is an analytical and transversal study. CD1a and FXIIIa markers were used to count the dendritic cells in skin samples. A predominance of CD1a and FXIIIa cells in the foveolar border lesion was observed as compared to the center area of the lesion. The prevalence of dendritic cells at the edge of the foveolar lesion can be justified by the pattern of inflammatory and immune response to M. leprae. The distribution of M. leprae may be concentrated in this region, promoting a greater antigenic exposure. The comparison between the center and the edge of the foveolar lesion has obtained a quantitative difference indicating a basic function of dendritic cells in response to M. leprae and, consequently, in the course of the disease.