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1.
J Infect Public Health ; 12(5): 656-659, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30904499

RESUMEN

BACKGROUND AND OBJECTIVE: Leprosy is a chronic slowly progressive infection caused by Mycobacterium leprae that primarily affects the skin and peripheral nerves. Lepromatous leprosy is characterized by absence of T-cell responses to M. leprae and advanced clinical disease. It is frequently associated with the presence of autoantibodies, which might be related to CD19+CD5+ and CD19+CD5- B lymphocyte percentages. Therefore, the aim of this study was to evaluate the percentages of CD19+CD5+ and CD19+CD5- B cell subsets as well as the total B cells in lepromatous leprosy patients. MATERIALS AND METHODS: Twenty lepromatous leprosy patients and ten healthy subjects served as control were included in this study. Venous blood samples were analyzed by flow cytometry to determine the B cell subsets and total B cell percentages. RESULTS: Compared to healthy controls, the percentages of CD19+CD5+ B cell subset and total B cells were found to be significantly higher in the patient group. While, the percentage of CD19+CD5- B cell subset was found to be higher in the patient group than the control without any significantly difference. Regarding the eye affection, the percentage of total B cells was observed to be significantly higher in affected patients compared to the non-affected group. CONCLUSION: The observed significant increases in CD19+CD5+ and total B cell percentages in patients with lepromatous leprosy suggests a possible role of these cells in the disorganized protective immune response as well as the development of eye complications in these patients.


Asunto(s)
Enfermedades Autoinmunes/inmunología , Subgrupos de Linfocitos B/inmunología , Antígenos CD5/inmunología , Lepra Lepromatosa/inmunología , Enfermedades Autoinmunes/microbiología , Estudios de Casos y Controles , Femenino , Citometría de Flujo , Humanos , Masculino , Mycobacterium leprae/inmunología , Factores de Riesgo , Piel/inmunología , Piel/microbiología
2.
Am J Trop Med Hyg ; 100(2): 377-385, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30652669

RESUMEN

Type 2 reaction (T2R) or erythema nodosum leprosum (ENL), a sudden episode of acute inflammation predominantly affecting lepromatous leprosy patients (LL), characterized by a reduced cellular immune response. This possibly indicates a close relationship between the onset of T2R and the altered frequency, and functional activity of T lymphocytes, particularly of memory subsets. This study performed ex vivo and in vitro characterizations of T cell blood subpopulations from LL patients with or without T2R. In addition, the evaluation of activity of these subpopulations was performed by analyzing the frequency of these cells producing IFN-γ, TNF, and IL-10 by flow cytometry. Furthermore, the expression of transcription factors, for the differentiation of T cells, were analyzed by quantitative real-time polymerase chain reaction. Our results showed an increased frequency of CD8+/TNF+ effector memory T cells (TEM) among T2Rs. Moreover, there was evidence of a reduced frequency of CD4 and CD8+ IFN-γ-producing cells in T2R, and a reduced expression of STAT4 and TBX21. Finally, a significant and positive correlation between bacteriological index (BI) of T2R patients and CD4+/TNF+ and CD4+/IFN-γ+ T cells was observed. Thus, negative correlation between BI and the frequency of CD4+/IL-10+ T cells was noted. These results suggest that CD8+/TNF+ TEM are primarily responsible for the transient alteration in the immune response to Mycobacterium leprae in ENL patients. Thus, our study improves our understanding of pathogenic mechanisms and might suggest new therapeutic approaches for leprosy.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Eritema Nudoso/inmunología , Lepra Lepromatosa/inmunología , Mycobacterium leprae/patogenicidad , Factor de Necrosis Tumoral alfa/inmunología , Adolescente , Adulto , Anciano , Linfocitos T CD4-Positivos/microbiología , Linfocitos T CD8-positivos/microbiología , Estudios de Casos y Controles , Eritema Nudoso/genética , Eritema Nudoso/patología , Femenino , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Humanos , Memoria Inmunológica , Inmunofenotipificación , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-10/genética , Interleucina-10/inmunología , Lepra Lepromatosa/genética , Lepra Lepromatosa/patología , Masculino , Persona de Mediana Edad , Mycobacterium leprae/crecimiento & desarrollo , Mycobacterium leprae/inmunología , Cultivo Primario de Células , Factor de Transcripción STAT4/genética , Factor de Transcripción STAT4/inmunología , Transducción de Señal , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/inmunología , Factor de Necrosis Tumoral alfa/genética
3.
PLoS Negl Trop Dis ; 13(1): e0007089, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30689631

RESUMEN

BACKGROUND: Leprosy is a treatable infectious disease caused by Mycobacterium leprae. However, there is additional morbidity from leprosy-associated pathologic immune reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL), which occur in 1 in 3 people with leprosy, even with effective treatment of M. leprae. There is currently no predictive marker in use to indicate which people with leprosy will develop these debilitating immune reactions. Our peripheral blood mononuclear cell (PBMC) transcriptome analysis revealed that activation of the classical complement pathway is common to both RR and ENL. Additionally, differential expression of immunoglobulin receptors and B cell receptors during RR and ENL support a role for the antibody-mediated immune response during both RR and ENL. In this study, we investigated B-cell immunophenotypes, total and M. leprae-specific antibodies, and complement levels in leprosy patients with and without RR or ENL. The objective was to determine the role of these immune mediators in pathogenesis and assess their potential as biomarkers of risk for immune reactions in people with leprosy. METHODOLOGY/FINDINGS: We followed newly diagnosed leprosy cases (n = 96) for two years for development of RR or ENL. They were compared with active RR (n = 35), active ENL (n = 29), and healthy household contacts (n = 14). People with leprosy who subsequently developed ENL had increased IgM, IgG1, and C3d-associated immune complexes with decreased complement 4 (C4) at leprosy diagnosis. People who developed RR also had decreased C4 at leprosy diagnosis. Additionally, elevated anti-M. leprae antibody levels were associated with subsequent RR or ENL. CONCLUSIONS: Differential co-receptor expression and immunoglobulin levels before and during immune reactions intimate a central role for humoral immunity in RR and ENL. Decreased C4 and elevated anti-M. leprae antibodies in people with new diagnosis of leprosy may be risk factors for subsequent development of leprosy immune reactions.


Asunto(s)
Anticuerpos Antibacterianos/sangre , Complemento C3d/análisis , Complemento C4/análisis , Eritema Nudoso/epidemiología , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Lepra Lepromatosa/epidemiología , Mycobacterium leprae/inmunología , Adulto , Anciano , Anticuerpos Antibacterianos/inmunología , Linfocitos B/inmunología , Complemento C3d/inmunología , Complemento C4/inmunología , Eritema Nudoso/sangre , Eritema Nudoso/inmunología , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunidad Activa/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Lepra Lepromatosa/sangre , Lepra Lepromatosa/inmunología , Masculino , Persona de Mediana Edad , Factores de Riesgo
4.
BMC Infect Dis ; 18(1): 576, 2018 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-30442123

RESUMEN

BACKGROUND: Since macrophages are one of the major cell types involved in the Mycobacterium leprae immune response, roles of the M1 and M2 macrophage subpopulations have been well defined. However, the role of M4 macrophages in leprosy or other infectious diseases caused by mycobacteria has not yet been clearly characterized. This study aimed to investigate the presence and potential role of M4 macrophages in the immunopathology of leprosy. METHODS: We analyzed the presence of M4 macrophage markers (CD68, MRP8, MMP7, IL-6, and TNF-α) in 33 leprosy skin lesion samples from 18 patients with tuberculoid leprosy and 15 with lepromatous leprosy by immunohistochemistry. RESULTS: The M4 phenotype was more strongly expressed in patients with the lepromatous form of the disease, indicating that this subpopulation is less effective in the elimination of the bacillus and consequently is associated with the evolution to one of the multibacillary clinical forms of infection. CONCLUSION: M4 macrophages are one of the cell types involved in the microbial response to M. leprae and probably are less effective in controlling bacillus replication, contributing to the evolution to the lepromatous form of the disease.


Asunto(s)
Lepra/metabolismo , Macrófagos/metabolismo , Mycobacterium leprae/inmunología , Enfermedades de la Piel/metabolismo , Piel/metabolismo , Adulto , Biomarcadores/metabolismo , Brasil , Femenino , Humanos , Inmunohistoquímica , Lepra/inmunología , Lepra/patología , Lepra Lepromatosa/inmunología , Lepra Lepromatosa/metabolismo , Lepra Lepromatosa/patología , Lepra Tuberculoide/inmunología , Lepra Tuberculoide/metabolismo , Lepra Tuberculoide/patología , Macrófagos/inmunología , Macrófagos/patología , Masculino , Piel/inmunología , Piel/patología , Enfermedades de la Piel/inmunología , Enfermedades de la Piel/microbiología , Enfermedades de la Piel/patología
5.
An Bras Dermatol ; 93(1): 123-125, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29641713

RESUMEN

Brazil is a country with a high prevalence of infectious diseases such as leprosy and leishmaniasis. However, coinfection of these diseases is still poorly understood. We report a case of a patient who presented with lepromatous leprosy and cutaneous-mucosal leishmaniasis at the same period. After clinical, laboratory, and histopathological diagnosis, the treatment was introduced and the patient showed important clinical improvement. He was followed in our outpatient clinic. Both pathologies play an important role in the immune system. Depending on the immune response profile of the host, diseases may present themselves in different ways. In this case, the patient showed a divergent immune response for each disease. We hypothesized that this response is specific for each pathogen.


Asunto(s)
Coinfección/complicaciones , Leishmaniasis Mucocutánea/complicaciones , Lepra Lepromatosa/complicaciones , Coinfección/inmunología , Coinfección/patología , Humanos , Inmunidad Celular/inmunología , Leishmaniasis Mucocutánea/inmunología , Leishmaniasis Mucocutánea/patología , Lepra Lepromatosa/inmunología , Lepra Lepromatosa/patología , Masculino , Persona de Mediana Edad
6.
Front Immunol ; 9: 246, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29487601

RESUMEN

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.


Asunto(s)
Antígenos de Diferenciación de Linfocitos B/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Interacciones Microbiota-Huesped/inmunología , Oxidorreductasas Intramoleculares/sangre , Lepra Lepromatosa/inmunología , Factores Inhibidores de la Migración de Macrófagos/sangre , Piel/inmunología , Adulto , Antígenos de Diferenciación de Linfocitos B/metabolismo , Biopsia , Estudios de Casos y Controles , Femenino , Voluntarios Sanos , Antígenos de Histocompatibilidad Clase II/metabolismo , Humanos , Inmunidad Celular , Oxidorreductasas Intramoleculares/inmunología , Oxidorreductasas Intramoleculares/metabolismo , Lepra Lepromatosa/sangre , Lepra Lepromatosa/patología , Factores Inhibidores de la Migración de Macrófagos/inmunología , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Masculino , Persona de Mediana Edad , Mycobacterium leprae/inmunología , Piel/citología , Piel/patología
8.
Acta Trop ; 183: 134-141, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29474830

RESUMEN

Erythema Nodosum Leprosum (ENL) occurs due to the immunological complication of multibacillary leprosy and is characterized by painful nodules and systemic compromising. It is usually recurrent and/or chronic and has both physical and economic impact on the patient, being a very important cause of disability. In addition, ENL is a major health problem in countries where leprosy is endemic. Therefore, adequate control of this condition is important. The management of ENL aims to control acute inflammation and neuritis and prevent the onset of new episodes. However, all currently available treatment modalities have one or two drawbacks and are not effective for all patients. Corticosteroid is the anti-inflammatory of choice in ENL but may cause dependence, especially for chronic patients. Thalidomide has a rapid action but its use is limited due the teratogenicity and neurotoxicity. Clofazimine and pentoxifylline have slow action and have important adverse effects. Finally, there is no pattern or guidelines for treating these patients, becoming more difficult to evaluate and to control this condition. This review aims to show the main drugs used in the treatment of ENL and the challenges in the management of the reaction.


Asunto(s)
Antiinflamatorios/uso terapéutico , Eritema Nudoso/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Leprostáticos/uso terapéutico , Lepra Lepromatosa/tratamiento farmacológico , Pentoxifilina/uso terapéutico , Talidomida/uso terapéutico , Eritema Nudoso/inmunología , Humanos , Inflamación , Lepra Lepromatosa/inmunología , Enfermedades Desatendidas/tratamiento farmacológico , Recurrencia , Inducción de Remisión , Resultado del Tratamiento
9.
An. bras. dermatol ; 93(1): 123-125, Jan.-Feb. 2018. graf
Artículo en Inglés | LILACS | ID: biblio-887166

RESUMEN

Abstract: Brazil is a country with a high prevalence of infectious diseases such as leprosy and leishmaniasis. However, coinfection of these diseases is still poorly understood. We report a case of a patient who presented with lepromatous leprosy and cutaneous-mucosal leishmaniasis at the same period. After clinical, laboratory, and histopathological diagnosis, the treatment was introduced and the patient showed important clinical improvement. He was followed in our outpatient clinic. Both pathologies play an important role in the immune system. Depending on the immune response profile of the host, diseases may present themselves in different ways. In this case, the patient showed a divergent immune response for each disease. We hypothesized that this response is specific for each pathogen.


Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Lepra Lepromatosa/complicaciones , Leishmaniasis Mucocutánea/complicaciones , Coinfección/complicaciones , Lepra Lepromatosa/inmunología , Lepra Lepromatosa/patología , Leishmaniasis Mucocutánea/inmunología , Leishmaniasis Mucocutánea/patología , Coinfección/inmunología , Coinfección/patología , Inmunidad Celular/inmunología
11.
Microb Pathog ; 113: 427-431, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29170041

RESUMEN

Leprosy caused by Mycobacterium leprae is characterized by a spectrum of clinical manifestations that are determined by the predominant immunological profile of the host. The recruitment of leukocytes to the sites of injury can influence the development of these profiles. Cell adhesion molecules such as ICAM-1, VCAM-1 and CD62E participate in this process and their expression is regulated by transcriptions factors such as NFκB. To correlate the expression of cell adhesion molecules and NFκB (p65) in leprosy lesions, 30 skin biopsies of patients with leprosy [16 with the tuberculoid (TT) or borderline tuberculoid (BT) forms and 14 with the lepromatous (LL) or borderline lepromatous (BL) forms] were analyzed by immunohistochemistry. A larger mean number of cells expressing VCAM-1 (BT/TT: 18.28 ± 1.4; BL/LL: 10.67 ± 1.2; p = 0.0002), ICAM-1 (BT/TT: 9.92 ± 1.1; BL/LL: 5.87 ± 1.0; p = 0.0084) and CD62E (BT/TT: 13.0 ± 1.5; BL/LL: 2.58 ± 0.3; p = 0.0001) were observed in BT and TT lesions. The mean number of cells expressing NFκB was similar in the two clinical forms (BT/TT: 2.21 ± 2.7; BL/LL: 2.35 ± 3.1;p = 0.9285). No significant correlation was observed between expression of the transcription factor and adhesion molecules analyzed. The synthesis of ICAM-1, VCAM-1 and CD62E depends on the activation of NFκB, which acts synergistically with other transcription factors. Adequate activation of intracellular signaling pathways results in the production of endothelial adhesion molecules, contributing to the recruitment of cells to the site of injury and thus eliciting an effective inflammatory response in the elimination of the bacillus.


Asunto(s)
Inmunohistoquímica , Lepra Lepromatosa/inmunología , Lepra Lepromatosa/patología , Factor de Transcripción ReIA/metabolismo , Factores de Transcripción/metabolismo , Biopsia , Selectina E/biosíntesis , Endotelio/patología , Humanos , Molécula 1 de Adhesión Intercelular/biosíntesis , Lepra Lepromatosa/microbiología , Leucocitos/inmunología , Leucocitos/microbiología , Microvasos , Mycobacterium leprae/patogenicidad , FN-kappa B/metabolismo , Piel/patología , Molécula 1 de Adhesión Celular Vascular/biosíntesis
12.
J Dtsch Dermatol Ges ; 15(8): 801-827, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28763601

RESUMEN

Leprosy is a chronic infectious disease caused by Mycobacterium (M.) leprae. Worldwide, 210,758 new cases were diagnosed in 2015. The highest incidence is found in India, Brazil, and Indonesia. While the exact route of transmission remains unknown, nasal droplet infection is thought to be most likely. The pathogen primarily affects the skin and peripheral nervous system. The disease course is determined by individual host immunity. Clinically, multibacillary lepromatous variants are distinguished from paucibacillary tuberculoid forms. Apart from the various characteristic skin lesions, the condition is marked by damage to the peripheral nervous system. Advanced disease is characterized by disfiguring mutilations. Current treatment options are based on WHO recommendations. Early treatment frequently results in complete remission without sequelae. While paucibacillary forms are treated with rifampicin and dapsone for at least six months, multibacillary leprosy is treated for at least twelve months, additionally requiring clofazimine. Leprosy reactions during therapy may considerably aggravate the disease course. Besides individual treatment, WHO-supported preventive measures and strategies play a key role in endemic areas.


Asunto(s)
Leprostáticos/uso terapéutico , Lepra Lepromatosa/diagnóstico , Lepra Lepromatosa/tratamiento farmacológico , Lepra Tuberculoide/diagnóstico , Lepra Tuberculoide/tratamiento farmacológico , Enfermedades Desatendidas , Adulto , Anciano , Niño , Clofazimina/efectos adversos , Clofazimina/uso terapéutico , Estudios Transversales , Dapsona/efectos adversos , Dapsona/uso terapéutico , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Adhesión a Directriz , Humanos , Inmunidad Celular/efectos de los fármacos , Lepra Dimorfa/diagnóstico , Lepra Dimorfa/tratamiento farmacológico , Lepra Dimorfa/epidemiología , Lepra Dimorfa/inmunología , Lepra Lepromatosa/epidemiología , Lepra Lepromatosa/inmunología , Lepra Tuberculoide/epidemiología , Lepra Tuberculoide/inmunología , Cuidados a Largo Plazo , Masculino , Rifampin/efectos adversos , Rifampin/uso terapéutico
13.
Cytokine ; 97: 42-48, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28570932

RESUMEN

Leprosy or Hansen's disease is a chronic infectious disease of the skin and nerves, caused by the intracellular bacilli Mycobacterium leprae. It is characterized by a spectrum of clinical forms depending on the host's immune response to M. leprae. Patients with tuberculoid (TT) leprosy have strong cell-mediated immunity (CMI) with elimination of the bacilli, whereas patients with lepromatous (LL) leprosy exhibit defective CMI to M. leprae. Despite advances in the understanding of the pathogenesis of leprosy and the development of new therapeutic strategies, there is a need for the identification of biomarkers which be used for early diagnosis and to discrimination between different forms of the disease, as prognostic markers. Here, we analyzed the serum levels of IL-1ß, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IFN-γ and TNF in order to address the contribution of these cytokines in late phase of M. leprae infection, and the impact of multidrug therapy (MDT). Our results demonstrated that patients of LL group presented higher expression of serum levels of inflammatory cytokines before MDT, while TT patients presented a balance between inflammatory and regulatory cytokines. MDT changes the profile of serum cytokines in M. leprae infected patients, as evidenced by the cytokine network, especially in TT patients. LL patients displayed a multifaceted cytokine system characterized by strong connecting axes involving inflammatory/regulatory molecules, while TT patients showed low involvement of regulatory cytokines in network overall. Cytokines can be identified as good biomarkers of the impact of MDT on the immune system and the effectiveness of treatment.


Asunto(s)
Citocinas/sangre , Lepra Lepromatosa/tratamiento farmacológico , Lepra Lepromatosa/inmunología , Biomarcadores/sangre , Quimioterapia Combinada , Humanos , Inmunidad Celular , Interferón gamma/sangre , Interleucina-10/sangre , Interleucina-12/sangre , Interleucina-13/sangre , Lepra Lepromatosa/sangre , Lepra Lepromatosa/fisiopatología , Mycobacterium leprae/efectos de los fármacos , Mycobacterium leprae/inmunología
15.
J Clin Pathol ; 70(6): 521-527, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27927694

RESUMEN

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)-ß 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-ß was observed in LL compared with TT. IL-4, IL-10 and TGF-ß 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.


Asunto(s)
Interleucina-9/metabolismo , Lepra/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Adulto , Estudios Transversales , Citocinas/metabolismo , Femenino , Humanos , Inmunidad Celular/inmunología , Lepra Lepromatosa/inmunología , Masculino , Mycobacterium leprae/inmunología
16.
Rev Alerg Mex ; 63(4): 413-419, 2016.
Artículo en Español | MEDLINE | ID: mdl-27795222

RESUMEN

BACKGROUND: Leprosy is a chronic granulomatous infection that affects skin and peripheral nerves. Its prevalence has declined, but is still observed mainly in poor rural areas. CASE REPORT: A male city dweller with photophobia and chronic dermatosis in the face: nodular and erythematous lesions, pustules, keratitis and entropion, partial eyebrows loss, and edema on eyelids, chin, and nose bridge. The rest of the body had no lesion or lymphadenopathy. Biopsy revealed Langhans giant cell proliferation in the superficial dermis without epidermal atrophy. BAAR staining for detection were positive, no Virschow cells were observed, and Fite-Franco staining (leprosy-specific) was negative. Cutaneous tuberculosis was diagnosed. Rifampicin/isoniazid/pyrazinamide and dialysate leukocyte extract were prescribed. A month later, the swelling had decreased significantly. Polymerase chain reaction (PCR) test was positive for Mycobacterium leprae. Flow cytometry showed CD4 count normalization. Long-term treatment with rifampicin, clofazimine, and dapsone was established. CONCLUSIONS: The host's immune response determines the clinical features of the disease: if response is bad there will be vacuolated macrophages filled with bacilli (lepromatous leprosy). Clinical and histopathological findings help typing.


Asunto(s)
Lepra Lepromatosa/inmunología , Humanos , Lepra Lepromatosa/patología , Masculino , Mycobacterium leprae/aislamiento & purificación , Tuberculosis Cutánea/diagnóstico
19.
JCI Insight ; 1(15): e88843, 2016 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-27699251

RESUMEN

Transcriptome profiles derived from the site of human disease have led to the identification of genes that contribute to pathogenesis, yet the complex mixture of cell types in these lesions has been an obstacle for defining specific mechanisms. Leprosy provides an outstanding model to study host defense and pathogenesis in a human infectious disease, given its clinical spectrum, which interrelates with the host immunologic and pathologic responses. Here, we investigated gene expression profiles derived from skin lesions for each clinical subtype of leprosy, analyzing gene coexpression modules by cell-type deconvolution. In lesions from tuberculoid leprosy patients, those with the self-limited form of the disease, dendritic cells were linked with MMP12 as part of a tissue remodeling network that contributes to granuloma formation. In lesions from lepromatous leprosy patients, those with disseminated disease, macrophages were linked with a gene network that programs phagocytosis. In erythema nodosum leprosum, neutrophil and endothelial cell gene networks were identified as part of the vasculitis that results in tissue injury. The present integrated computational approach provides a systems approach toward identifying cell-defined functional networks that contribute to host defense and immunopathology at the site of human infectious disease.


Asunto(s)
Redes Reguladoras de Genes , Lepra/genética , Lepra/inmunología , Adolescente , Adulto , Eritema Nudoso/genética , Eritema Nudoso/inmunología , Femenino , Humanos , Lepra Lepromatosa/genética , Lepra Lepromatosa/inmunología , Lepra Tuberculoide/genética , Lepra Tuberculoide/inmunología , Masculino , Persona de Mediana Edad , Transcriptoma , Adulto Joven
20.
PLoS Negl Trop Dis ; 10(8): e0004955, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27556927

RESUMEN

Erythema Nodosum Leprosum (ENL) is an immune reaction in leprosy that aggravates the patient´s clinical condition. ENL presents systemic symptoms of an acute infectious syndrome with high leukocytosis and intense malaise clinically similar to sepsis. The treatment of ENL patients requires immunosuppression and thus needs to be early and efficient to prevent both disabilities and permanent nerve damage. Some patients experience multiple episodes of ENL and prolonged use of immunosuppressive drugs may lead to serious adverse effects. Thalidomide treatment is extremely effective at ameliorating ENL symptoms. Several mechanisms have been proposed to explain the efficacy of thalidomide in ENL, including the inhibition of TNF production. Given its teratogenicity, thalidomide is prohibitive for women of childbearing age. A rational search for molecular targets during ENL episodes is essential to better understand the disease mechanisms involved, which may also lead to the discovery of new drugs and diagnostic tests. Previous studies have demonstrated that IFN-γ and GM-CSF, involved in the induction of CD64 expression, increase during ENL. The aim of the present study was to investigate CD64 expression during ENL and whether thalidomide treatment modulated its expression. Leprosy patients were allocated to one of five groups: (1) Lepromatous leprosy, (2) Borderline leprosy, (3) Reversal reaction, (4) ENL, and (5) ENL 7 days after thalidomide treatment. The present study demonstrated that CD64 mRNA and protein were expressed in ENL lesions and that thalidomide treatment reduced CD64 expression and neutrophil infiltrates-a hallmark of ENL. We also showed that ENL blood neutrophils exclusively expressed CD64 on the cell surface and that thalidomide diminished overall expression. Patient classification based on clinical symptoms found that severe ENL presented high levels of neutrophil CD64. Collectively, these data revealed that ENL neutrophils express CD64, presumably contributing to the immunopathogenesis of the disease.


Asunto(s)
Eritema Nudoso/inmunología , Leprostáticos/uso terapéutico , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Receptores de IgG/genética , Talidomida/uso terapéutico , Adolescente , Adulto , Anciano , Biopsia , Eritema Nudoso/diagnóstico , Eritema Nudoso/tratamiento farmacológico , Eritema Nudoso/microbiología , Femenino , Humanos , Lepra Dimorfa/tratamiento farmacológico , Lepra Dimorfa/inmunología , Lepra Dimorfa/microbiología , Lepra Lepromatosa/tratamiento farmacológico , Lepra Lepromatosa/inmunología , Lepra Lepromatosa/microbiología , Masculino , Persona de Mediana Edad , Receptores de IgG/inmunología , Piel/microbiología , Piel/patología , Adulto Joven
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