RESUMEN
The parasite Leishmania (Viannia) braziliensis is widely distributed in Brazil and is one of the main species associated with human cases of different forms of tegumentary leishmaniasis (TL) such as cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML). The mechanisms underlying the pathogenesis of TL are still not fully understood, but it is known that factors related to the host and the parasite act in a synergistic and relevant way to direct the response to the infection. In the host, macrophages have a central connection with the parasite and play a fundamental role in the defense of the organism due to their ability to destroy intracellular parasites and present antigens. In the parasite, some intrinsic factors related to the species or even the strain analyzed are fundamental for the outcome of the disease. One of them is the presence of Leishmania RNA Virus 1 (LRV1), an endosymbiont virus that parasitizes some species of Leishmania that triggers a cascade of signals leading to a more severe TL phenotype, such as ML. One of the strategies for understanding factors associated with the immune response generated after Leishmania/host interaction is through the analysis of molecular patterns after infection. Thus, the gene expression profile in human monocyte-derived macrophages obtained from healthy donors infected in vitro with L. braziliensis positive (LbLRV1+) and negative (LbLRV1-) for LRV1 was evaluated. For this, the microarray assay was used and 162 differentially expressed genes were identified in the comparison LbLRV1+ vs. LbLRV1-, 126 upregulated genes for the type I and II interferons (IFN) signaling pathway, oligoadenylate synthase OAS/RNAse L, non-genomic actions of vitamin D3 and RIG-I type receptors, and 36 down-regulated. The top 10 downregulated genes along with the top 10 upregulated genes were considered for analysis. Type I interferon (IFNI)- and OAS-related pathways results were validated by RT-qPCR and Th1/Th2/Th17 cytokines were analyzed by Cytometric Bead Array (CBA) and enzyme-linked immunosorbent assay (ELISA). The microarray results validated by RT-qPCR showed differential expression of genes related to IFNI-mediated pathways with overexpression of different genes in cells infected with LbLRV1+ compared to LbLRV1- and to the control. No significant differences were found in cytokine levels between LbLRV1+ vs. LbLRV1- and control. The data suggest the activation of gene signaling pathways associated with the presence of LRV1 has not yet been reported so far. This study demonstrates, for the first time, the activation of the OAS/RNase L signaling pathway and the non-genomic actions of vitamin D3 when comparing infections with LbLRV1+ versus LbLRV1- and the control. This finding emphasizes the role of LRV1 in directing the host's immune response after infection, underlining the importance of identifying LRV1 in patients with TL to assess disease progression.
Asunto(s)
Leishmania braziliensis , Leishmaniavirus , Macrófagos , Humanos , Leishmania braziliensis/genética , Leishmania braziliensis/inmunología , Macrófagos/inmunología , Macrófagos/virología , Leishmaniavirus/genética , Perfilación de la Expresión Génica , Leishmaniasis Cutánea/inmunología , Brasil , Simbiosis , Citocinas/metabolismo , Citocinas/genética , Transcriptoma , Leishmaniasis Mucocutánea/inmunología , Leishmaniasis Mucocutánea/parasitologíaRESUMEN
Leishmaniasis, a parasitic disease produced by a protozoan of the genus Leishmania, is triggered by the bite of an infected sandfly. It is endemic in tropical and subtropical areas of the Americas, places of poor socioeconomic health conditions and malnutrition. These conditions favor the entry of other pathogens such as the dimorphic fungus Paracoccidioides brasiliensis, responsible for Paracoccidioidomycosis (PCM), deep mycosis of inhalatory entry that initially affects the lungs; then skin, mucous membranes, lymph nodes and adrenal glands. The association of reported cases of Leishmaniasis and Paracoccidiodoimicosis in the same patient is infrequent. We point out the importance of the multidisciplinary approach for the correct diagnosis and treatment.
Asunto(s)
Humanos , Masculino , Anciano , Paracoccidioidomicosis/diagnóstico , Factores Socioeconómicos , Leishmaniasis Mucocutánea/inmunología , Anfotericina B/uso terapéutico , Itraconazol/uso terapéutico , Enfermedades Endémicas/prevención & control , DesnutriciónRESUMEN
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/inmunologíaRESUMEN
ABSTRACT Rheumatoid arthritis (RA) is a chronic condition that is frequent in patients living in tropical areas exposed to leishmaniasis. RA therapy involves immunosuppressant drugs such as methotrexate (MTX), monoclonal antibodies (mAbs) and prednisone. We report an unusual presentation of cutaneous (CL) or mucocutaneous leishmaniasis (ML) in RA patients from an endemic area of leishmaniasis. A 51-year-old woman noted a cutaneous ulcer on her left ankle during MTX and prednisone RA therapy. Initially diagnosed as a venous stasis ulcer, the aspirate of the injury revealed the presence of Leishmania DNA. A 73-year-old woman presenting non-ulcerated, infiltrated and painful erythematous nodules inside her nostrils while receiving MTX, anti-TNF mAb, and prednisone for RA, had also the aspirate of injuries showing the presence of Leishmania DNA. Both patients healed after the therapy with liposomal amphotericin. The RA therapy has changed to low-dose prednisone, without further reactivation episodes. Both cases suggest that CL or ML can reactivate after administration of an immunosuppressant for RA treatment. Therefore, immunosuppressive treatments for RA should be carefully prescribed in patients from endemic areas or with a history of CL and ML.
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Anciano , Antirreumáticos/efectos adversos , Inmunosupresores/efectos adversos , Leishmaniasis Cutánea/etiología , Leishmania/aislamiento & purificación , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inmunología , ADN Protozoario/análisis , Inmunosupresores/uso terapéutico , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Mucocutánea/inmunología , Leishmania/genética , RecurrenciaRESUMEN
Es importante conocer si la variabilidad de especies de Leishmania circulantes en una región afecta la performance de las pruebas de ELISA estandarizadas para el diagnostico de la leishmaniasis. El objetivo de este trabajo fue analizar la reactividad de la prueba de ELISA utilizando homogenados de promastigotes de Leishmania (V.) braziliensis (ELISAb), L (L) amazonensis (ELISAa) y L (V.) guyanensis (ELISAg) frente a distintos grupos de sueros. Se estudiaron muestras de personas con leishmaniasis cutánea (n = 37), leishmaniasis mucocutánea (n = 8), no infectados (n = 52), infectadas por Trypanosoma cruzi (n = 11) e infecciones mixtas (n = 14). Se calcularon las sensibilidades, especificidades, cut off, valores predictivos, y se compararon las tres pruebas usando ANOVA, índice de concordancia kappa, comparación de curvas ROC e intervalos de confianza construidos por el método de bootstrap. Se encontraron diferencias significativas al comparar los niveles de DO de los sueros de pacientes con leishmaniasis cutánea respecto a los controles negativos, pero no se encontraron diferencias entre pruebas. Las sensibilidades calculadas fueron de 84.6% para ELISAb y ELISAa y de 88.5 para ELISAg, mientras que el valor de especificidad para las tres pruebas fue de 96.2. El índice de concordancia kappa y la comparación de curvas ROC mostraron performances similares para las tres pruebas (p = 0.225). La elevada reactividad obtenida para estas ELISAs frente a sueros de pacientes con leishmaniasis mucocutánea indica un importante potencial de esta técnica como complemento en el diagnóstico de la enfermedad.
It is important to know whether the variability of species of Leishmania parasites circulating in a region affects the performance of the ELISA test for the diagnosis of leishmaniasis. Therefore, the aim of this study was to analyze the reactivity of the ELISA using homogenates of promastigotes of Leishmania (V.) braziliensis (ELISAb), Leishmania (L) amazonensis (ELISAa) and Leishmania (V.) guyanensis (ELISAg) against different sera groups. Samples from individuals with cutaneous leishmaniasis (n = 37), mucocutaneous leishmaniasis (n = 8), healthy controls (n = 52), persons infected with Trypanosoma cruzi (n = 11) and mixed infections (n = 14) were included in the study. We calculated sensitivities, specificities, cut offs, and predictive values for the three tests and compared them using ANOVA, kappa index, ROC curves comparison, and confidence intervals calculated by the bootstrap method. Significant differences were found when comparing the OD levels of sera from patients with cutaneous leishmaniasis against healthy controls, but there were no differences when comparing the different ELISAs. The sensitivities calculated for ELISAb and ELISAa were 84.6 and of 88.5% for ELISAg, while the value of specificity for the three tests was 96.2. The kappa index (0.87) and comparison of ROC curves showed similar performance for the three ELISAs (p = 0.225). The high reactivity obtained for these ELISAs in sera of patients with mucocutaneous leishmaniasis indicates this test as an important complement in the diagnosis of the disease.
Asunto(s)
Humanos , Antígenos de Protozoos/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Leishmania/inmunología , Leishmaniasis Cutánea/diagnóstico , Proteínas Protozoarias/sangre , Análisis de Varianza , Intervalos de Confianza , Enfermedad de Chagas/inmunología , Leishmania braziliensis/inmunología , Leishmania guyanensis/inmunología , Leishmania mexicana/inmunología , Leishmaniasis Cutánea/inmunología , Leishmaniasis Mucocutánea/diagnóstico , Leishmaniasis Mucocutánea/inmunología , Sensibilidad y Especificidad , Trypanosoma cruzi/químicaRESUMEN
HIV coinfection modifies the clinical course of leishmaniasis by promoting a Th2 pattern of cytokine production. However, little information is available regarding the lymphocytic response in untreated coinfected patients. This work presents the immunophenotyping of Leishmania-stimulated T cells from a treatment-naÏve HIV+ patient with ML. Leishmania braziliensis antigens induced CD69 expression on CD3+CD4+ and CD3+CD8+ cells. It also increased IL-4 intracellular staining on CD3+CD4+GATA3- population and decreased the percentage of CD3+CD4+IL-17+ cells. This suggests that modulations in the IL-4R/STAT6 pathway and the Th17 population may serve as parasitic evasion mechanisms in HIV/ML. Further studies are required to confirm these results.
A co-infecção por HIV modifica o curso clínico da leishmaniose ao promover aumento no perfil Th2 de produção de citocinas. No entanto, há pouca informação a respeito da resposta linfocitária em pacientes co-infectados sem tratamento. Neste trabalho, foi realizada a imunofenotipagem de células T estimuladas com antígenos de Leishmania braziliensis em paciente não tratado HIV+ e com leishmaniose mucosa. Os resultados mostraram aumento na expressão de CD69 em células CD3+CD4+ e CD3+CD8+. Além disso, foi observado aumento de IL-4 na população de linfócitos CD3+CD4+GATA3- e diminuição no percentual de células CD3+CD4+IL-17+. Estes resultados sugerem que a modulação da via IL-4R/STAT6 e da população de células Th17 funcione como mecanismo de evasão parasitária em HIV/LM. Estudos futuros são necessários para confirmar estes resultados.
Asunto(s)
Adulto , Humanos , Masculino , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Inmunofenotipificación , Leishmania braziliensis/inmunología , Leishmaniasis Mucocutánea/inmunología , Linfocitos T/inmunología , Linfocitos T/clasificaciónRESUMEN
American tegumentary leishmaniasis presents as two major clinical forms: localized cutaneous leishmaniasis (LCL) and mucocutaneous leishmaniasis (MCL). The immune response in leishmaniasis is efficiently evaluated by the response to Leishmania antigen through the Montenegro skin test (MST). Both LCL and MCL present positive response to MST, indicating that the patients present cell-mediated immunity against the parasite - Leishmania. In spite of the presence of immunity in MCL, this is not sufficient to stop disease progression and prevent resistance to treatment. In this study we demonstrated interleukin (IL) 2, 4, 5 and interferon (IFN) gamma expression in biopsies of MST of ten patients with American tegumentary leishmaniasis. The obtained results were compared between LCL (n = 5) and MCL (n = 5) patients. The MST of MCL patients displayed a higher expression of IL-2, IL-4 and IL-5, in comparison to LCL. There was no significant difference in IFN-gamma expression between groups. The obtained results suggest the role of IL-4 and IL-5 in the maintenance of the immunopathogenic mechanism of the destructive lesions that characterize MCL.
A leishmaniose tegumentar americana apresenta duas formas clínicas mais comuns: a leishmaniose cutânea localizada e a leishmaniose cutâneo-mucosa. A imunidade da leishmaniose é avaliada pela resposta ao antígeno Leishmania através da Intradermorreação de Montenegro. Estas duas formas apresentam resposta positiva, indicando que o paciente apresenta imunidade celular contra o parasita Leishmania. Apesar da presença da imunidade celular na leishmaniose cutâneo-mucosa, esta não é suficiente para barrar a progressão da doença e a resistência ao tratamento. Neste estudo, detectamos quatro citocinas por imunohistoquímica, IL-2, IL-4, IL-5 e IFN-gama nas biópsias da intradermorreação de Montenegro de pacientes com leishmaniose tegumentar americana (n = 10), cinco com leishmaniose cutânea e cinco com cutâneo-mucosa. Os resultados mostraram uma alta expressão significativa de IL-2, IL-4, IL-5 na leishmaniose cutâneo-mucosa comparada com a leishmaniose cutânea localizada, mas sem diferença significante na expressão do IFN-γ entre os grupos. Estes resultados sugerem a importância da participação da citocina IL-4 e IL-5 na manutenção do mecanismo imunopatogênico das lesões destrutivas da forma cutâneo-mucosa.
Asunto(s)
Adulto , Anciano de 80 o más Años , Animales , Femenino , Humanos , Persona de Mediana Edad , Adulto Joven , Interferón gamma/análisis , Interleucinas/análisis , Leishmaniasis Cutánea/inmunología , Inmunohistoquímica , Pruebas Intradérmicas , Leishmaniasis Mucocutánea/inmunología , Adulto JovenRESUMEN
This work analyzed the histopathology and epidermal Langerhans cells (LC) of Montenegro skin test (MST) in patients with American tegumentary leishmaniasis (ATL) in order to in situ characterize and compare the immunological reaction of the two major clinical forms of ATL, localized cutaneous leishmaniasis (LCL) and mucocutaneous leishmaniasis (MCL). MST histopathology of both LCL and MCL showed superficial and deep perivascular inflammatory infiltrate composed mainly of lymphocytes and histiocytes. Epidermal LC population was higher in MST biopsies taken from LCL patients when compared to MCL group, at 48 and 72 hours after antigen inoculation. Increased number of epidermal LC displayed in MST biopsies of LCL patients represents specific cellular immunity against parasites. The decrease of LC in MST biopsies of MCL patients does not necessarily indicate a worse specific cellular immunity in this clinical form of leishmaniasis.
Este trabalho analisou e quantificou as células de Langerhans e as características histopatológicas da reação de Montenegro nos pacientes com leishmaniose tegumentar americana (LTA) para caracterizar seu comportamento imunológico nas duas formas clínicas mais comuns da LTA, a leishmaniose cutânea localizada (LCL) e a leishmaniose cutâneo-mucosa (LCM). O exame histopatológico apresentou infiltrado inflamatório perivascular superficial e profundo, com predomínio de histiócitos e linfócitos, sem diferença significante entre as duas formas da doença. O resultado da quantificação das CL apresentou aumento das CL na LCL e diminuição na LCM em 48 e 72 horas após a inoculação do antígeno (p < 0,001). O aumento das células de Langerhans epidérmicas na reação de Montenegro da LCL demonstra a presença de imunidade celular específica, enquanto a diminuição das mesmas células na LCM não necessariamente demonstra uma diminuição da imunidade celular específica.
Asunto(s)
Animales , Humanos , Células de Langerhans/inmunología , Leishmaniasis Cutánea/parasitología , Pruebas Cutáneas/métodos , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/patología , Leishmaniasis Mucocutánea/inmunología , Leishmaniasis Mucocutánea/parasitología , Leishmaniasis Mucocutánea/patologíaRESUMEN
Total antigen from Leishmania (Leishmania) amazonensis and isolates from the Leishmania braziliensis complex, along with their respective antigenic fractions obtained by affinity chromatography on concanavalin-A-Sepharose and jacalin-agarose columns evaluated using immunoenzymatic ELISA assay. For this, serum samples from 229 patients were used, grouped as American tegmental leishmaniasis (nº=58), visceral leishmaniasis (nº=28), Chagas disease (nº=49), malaria (nº=32), tuberculosis (nº=13) and healthy volunteers (nº=49). Samples from American tegmentary leishmaniasis showed higher reactivity with antigens isolated from the Leishmania braziliensis complex than with antigens from Leishmania amazonensis (p<0.001). ELISA assays showed a sensitivity range from 60 percent to 95 percent with antigens isolated from the Leishmania braziliensis complex. There was marked nonspecific reactivity among serum samples with the use of antigenic fractions binding with concanavalin-A and jacalin from both Leishmania complexes, in comparison with other antigens (p<0.001). The results presented in this study suggest that the use of homologous antigens increases the efficiency of anti-Leishmania immunoglobulin detection, which may be very valuable for diagnostic purposes.
Antígeno total de Leishmania (Leishmania) amazonensis e isolado do complexo Leishmania brazilienis, assim como suas respectivas frações antigênicas obtidas por cromatografia de afinidade em coluna de concanavalina-A ligada a sepharose e Jacalina ligada a agarose foram avaliadas por ensaio imunoenzimático ELISA. Para tanto, foram utilizadas amostras de soros de 229 pacientes agrupadas em leishmaniose tegumentar americana (nº=58), leishmaniose visceral (nº=28), doença de Chagas (nº=49), malaria (nº=32), tuberculose (nº=13) e voluntários saudáveis (nº=49). Houve maior reatividade das amostras de leishmaniose tegumentar americana com a utilização dos antígenos obtidos do isolado do complexo Leishmania braziliensis quando comparado com antígenos de Leishmania amazonensis (p<0,001). Observou-se ainda que a sensibilidade do teste ELISA variou de 60 a 95 por cento entre os antígenos obtidos do isolado do complexo Leishmania braziliensis. Houve acentuada reatividade inespecífica das amostras de soros com a utilização das frações antigênicas ligantes de Concanavalina-A e Jacalina de ambos os complexos Leishmania em comparação aos demais antígenos (p<0,001). Os resultados apresentados no presente trabalho sugerem que a utilização de antígenos homólogos aumentam a eficiência de detecção de imunoglobulina anti-Leishmania o que pode ser de grande valia para o propósito de diagnóstico.
Asunto(s)
Animales , Humanos , Antígenos Helmínticos , Leishmania braziliensis/inmunología , Leishmania mexicana/inmunología , Leishmaniasis Mucocutánea/diagnóstico , Leishmaniasis Visceral/diagnóstico , Antígenos Helmínticos/aislamiento & purificación , Estudios de Casos y Controles , Cromatografía de Afinidad , Reacciones Cruzadas , Enfermedad de Chagas/inmunología , Ensayo de Inmunoadsorción Enzimática , Leishmaniasis Mucocutánea/inmunología , Leishmaniasis Visceral/inmunología , Malaria/inmunología , Lectinas de Plantas , Sensibilidad y Especificidad , Sefarosa/análogos & derivados , Sefarosa , Tuberculosis/inmunologíaRESUMEN
Na infecção humana por Leishmania há uma complexa interação parasito-hospedeiro, levando a uma variedade de formas clínicas. Em áreas de transmissão de L. braziliensis, cerca de 3 por cento dos pacientes com leishmaniose cutânea desenvolvem a forma mucosa da doença concomitantemente ou após cicatrização da ulcera. Células mononucleares do sangue periférico (CMSP) de pacientes com LM secretam maiores níveis de IFN-y do que as de pacientes com LC quando estimuladas com antígeno solúvel de leishmania (SLA). A presente tese é composta de 4 trabalhos e teve objetivo principal caracterizar a resposta imune de pacientes com LM e LC em células de sangue periférico e no tecido, e determinar fatores que possam estar envolvidos na resposta inflamatória exacerbada de pacientes com LM. Análise por citometria de fluxo demonstrou que a célula CD4+ é a principal célula produtora de IFN-y em pacientes com LC ou LM. (...) O presente estudo mostrou que pacientes com LM apresentam uma maior freqüencia de células CD4+ ativadas maior do que pacientes com LC. Essas células não são propriamente moduladas por antagonistas de citocinas envolvidas em diferenciação e proliferação linfocitária ou por antígenos que induzem IL-10, contribuindo também para este aspecto uma menor expressão de IL-10.
Asunto(s)
Leishmaniasis Mucocutánea/inmunología , Inmunidad MucosaRESUMEN
The objective of the present study is to describe two cases of dogs with mucocutaneous lesions caused by Leishmania spp. Both dogs presented destruction of the nasal septum, hyperemia with soft palate edema and barking alteration due to laryngeal compromise. Biopsies were taken from the lesion border and Leishmania spp. amastigotes were seen in the imprints. The dogs presented positive serology when complex soluble antigen from Leishmania mexicana was used. One of the dogs was also suspected to be infected by Trypanosoma cruzi as suggested by its positive reaction with a purified specific antigen, Ag163B6-cruzipain. Most of the studies concerning leishmaniosis in dogs have described the cutaneous form of this disease in close association with human cases of Leishmania infection instead of the mucocutaneous form described herein. The presence of dogs with mucocutaneous leishmaniosis alerts on an increase of the prevalence of this form in humans, which can cause deforming lesions, alterations of the speech and even an inadequate nutrition due to difficulties in deglutition.
Asunto(s)
Animales , Perros , Humanos , Masculino , Enfermedades de los Perros/epidemiología , Leishmaniasis Mucocutánea/veterinaria , Anticuerpos Antiprotozoarios/sangre , Argentina , Biopsia , Clima , Brotes de Enfermedades , Reservorios de Enfermedades , Enfermedad de Chagas/complicaciones , Enfermedad de Chagas/parasitología , Enfermedad de Chagas/veterinaria , Enfermedades de los Perros/inmunología , Enfermedades de los Perros/parasitología , Enfermedades de los Perros/patología , Leishmania mexicana , Leishmaniasis Mucocutánea/complicaciones , Leishmaniasis Mucocutánea/epidemiología , Leishmaniasis Mucocutánea/inmunología , Leishmaniasis Mucocutánea/parasitología , Leishmaniasis Mucocutánea/patología , Trypanosoma cruziRESUMEN
Purpose. To develop an animal model for studying mucocutaneous leishmaniasis. Methods. The hind footpad of C57B1/6j inbred mice was experimentally infected with 10(7) Leishmania (Leishmania) amazonensis promastigote and the skin was studied through ligh and electron transmission microscopy and immunohistochemistry (PAP) techniques. Results. There were morphological evidences of cellular immune mechanisms and hypersensitivity reaction after eight weeks of infection and metastasis and well shaped parasites at ultrastructural level by fifty-one weeks post infection. Relapse of infection with mucosa lesions occurred around the 50th week after inoculation. Conclusion. The use of this animal model in long term follow up could be an useful experimental model for human mucocutaneous leishmaniasis.
Asunto(s)
Animales , Femenino , Ratones , Piel/ultraestructura , Leishmaniasis Mucocutánea/patología , Leishmania/inmunología , Antígenos de Protozoos , Inmunohistoquímica , Microscopía Electrónica , Leishmaniasis Mucocutánea/inmunología , Estudios de Seguimiento , Modelos Animales de Enfermedad , Ratones Endogámicos C57BLRESUMEN
An atypical case of acquired immunodeficiency syndrome-associated mucocutaneous lesions due to Leishmania braziliensis is described. Many vacuolated macrophages laden with amastigote forms of the parasite were found in the lesions. Leishmanin skin test and serology for leishmaniasis were both negative. The patient was resistant to therapy with conventional drugs (antimonial and amphotericin B). Interestingly, remission of lesions was achieved after an alternative combined therapy of antimonial associated with immunotherapy (whole promastigote antigens). Peripheral blood mononuclear cells were separated and stimulated in vitro with Leishmania antigens to test the lymphoproliferative responses (LPR). Before the combined immunochemotherapy, the LPR to leishmanial antigens was negligible (stimulation index - SI=1.4). After the first course of combined therapy it became positive (SI=4.17). The antigen responding cells were predominantly T-cells (47.5 percent) most of them with CD8+ phenotype (33 percent). Very low CD4+ cells (2.2 percent) percentages were detected. The increased T-cell responsiveness to leishmanial antigens after combined therapy was accompanied by interferon-g (IFN-g) production as observed in the cell culture supernatants. In this patient, healing of the leishmaniasis lesions was associated with the induction of a specific T-cell immune response, characterized by the production of IFN-g and the predominance of the CD8+ phenotype among the Leishmania-reactive T-cells
Asunto(s)
Persona de Mediana Edad , Humanos , Masculino , Síndrome de Inmunodeficiencia Adquirida/terapia , Inmunoterapia , Leishmania braziliensis , Leishmaniasis Mucocutánea/terapia , Linfocitos T/inmunología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/inmunología , Inmunidad Celular , Leishmaniasis Mucocutánea/inmunologíaRESUMEN
La alta incidencia de leishmaniasis en las áreas andinas, tropicales y subtropicales de nuestro país ha sido motivación para poder hacer un enfoque global y profundo, que la información que hasta ahora nos había llegado. Creímos necesario hacer una revisión clara y objetiva de la realidad de la misma, así como también tratar de establecer una clínica mucho más amplia sobre la enfermedad, ya que como sabemos son la mayor parte, entidades o proyectos extranjeros los que se han encargado de recabar información estudios y avances en la lucha contra esta enfermedad. De la misma manera hemos tratado de recoger la mayor cantidad de datos acerca de la inmunología, diagnóstico y tratamiento, que creemos va ayudar a la mayor...
Asunto(s)
Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/terapia , Leishmaniasis Mucocutánea/diagnóstico , Leishmaniasis Mucocutánea/inmunología , Leishmaniasis Mucocutánea/terapia , ÚlceraRESUMEN
La leshmaniasis es producida por un protozoo, trasmitida por muchos mosquitos hematófagos (Lutzomia brasiliensis), artrópodos (Rhipicephalus turanicus) y probablemente triatomideos (Triatoma infestans, Pansterongilus infestans). En Bolivia existen tres formas de leishmaniasis: cutánea, mucocutánea y visceral, producidas por el mismo agente etiológico, con tres diferentes fases evolutivas relacionadas con mecanismos inmunológicos dependientes de muchos factores. Las tres responden a diversas drogas, a veces inespecíficas, que son empleadas para otras enfermedades (plasmodios, trichomonas, giardias, hongos y bacilos de Koch). Las sales antimoniales pentavalentes son las más comúnmente usadas, con resultados variables, a veces adversos, por su toxicidad, ineficacia ineficiencia y, sobre todo, resistencia y difícil manejo. Se ha demostrado que la L. cutánea tratada con glucantime, anfotericina B y otros presenta posteriormente lesiones mucocutáneas. Por otro lado, leishmaniosos que curaron espontáneamente han mostrado lesiones secundarias en forma ocasional. Lo que demuestra que en esta enfermedad existe una falla inmunológica, razón por la que usamos un inmunomodulador (DECARIS-clorhidrato de levamisol-, que es un antiparasitario), con buenos resultados (95 por ciento de éxito), sobre todo por su bajo costo, uso cómodo y efectos colaterales mínimos. Finalmente concluimos que en el momento actual no existe un leishmanicida eficaz para el tratamiento de esta enfermedad. El tratamiento inmunológico parece ser muy prometedor
Asunto(s)
Humanos , Alopurinol/uso terapéutico , Gluconato de Sodio Antimonio/uso terapéutico , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Mucocutánea/tratamiento farmacológico , Leishmaniasis/tratamiento farmacológico , Levamisol/uso terapéutico , Alopurinol/administración & dosificación , Gluconato de Sodio Antimonio/administración & dosificación , Gluconato de Sodio Antimonio/efectos adversos , Antiparasitarios/uso terapéutico , Bolivia/epidemiología , Diagnóstico Diferencial , Vectores de Enfermedades/clasificación , Interferón gamma/administración & dosificación , Interferón gamma/uso terapéutico , Itraconazol/administración & dosificación , Itraconazol/uso terapéutico , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/inmunología , Leishmaniasis Mucocutánea/diagnóstico , Leishmaniasis Mucocutánea/inmunología , Leishmaniasis/patología , Leishmaniasis/transmisión , Leishmania/clasificación , Levamisol/administración & dosificación , Metronidazol/administración & dosificación , Metronidazol/uso terapéuticoRESUMEN
We have detected antibodies, in the sera of Chagas disease, Kala-azar and Mucocutaneous leishmaniasis patients, that bind multiple antigens shared between the three causative agents. The Chagas disease sera showed 98 to 100 positive results by ELISA when the Leishmania braziliensis and Leishmania chagasi antigens were used, respectively. The Kala-azar sera showed 100 positive results with Trypanosoma cruzi or L. braziliensis antigens by immunofluorescence assays. The antibodies in the sera of Mucocutaneous leishmaniasis patients showed 100 positive results by ELISA assays with T. cruzi or L. chagasi antigens. Furthermore, the direct agglutination of L. chagasi promastigotes showed that 95 of Kala-azar and 35 of Mucocutaneous leishmaniasis sera agglutinated the parasite in dilutions above 1:512. In contrast, 15 of Chagas sera agglutinated the parasite in dilutions 1:16 and below. Western blot analysis showed that the Chagas sera that formed at least 24 bands with the T. cruzi also formed 13 bands with the L. chagasi and 17 bands with the L. braziliensis. The Kala-azar sera that recognized at least 29 bands with the homologous antigen also formed 14 bands with the T. cruzi and 10 bands with the L. braziliensis antigens. Finally, the Mucocutaneous leishmaniasis sera that formed at least 17 bands with the homologous antigen also formed 10 bands with the T. cruzi and four bands with the L. chagasi antigens. These results indicate the presence of common antigenic determinants in several protozoal proteins and, therefore, explain the serologic cross-reactions reported here.
Asunto(s)
Humanos , Animales , Leishmaniasis Visceral , Anticuerpos Antiprotozoarios/inmunología , Enfermedad de Chagas/inmunología , Leishmaniasis Mucocutánea/inmunología , Trypanosoma cruzi , Leishmania braziliensis , Leishmania infantum , Leishmaniasis Visceral , Anticuerpos Antiprotozoarios/sangre , Enfermedad de Chagas/sangre , Leishmaniasis Mucocutánea/sangre , Reacciones CruzadasRESUMEN
Delayed-type hypersensitivity (DTH) and antibodies against Leishmania have been studied in 207 Venezuelan patients with localized, muco-cutaneous and diffuse forms of American cutaneous leishmaniasis, representing the clinical spectrum of this disease. Muco-cutaneous disease appears to be related to inadequate immunomodulation or defective killing mechanisms; about 40 percent of these patients show exaggerated DTH, which is inversely related to antibody levels and is more pronounced in less extensive lesions. Patients with diffuse disease present severe antigen-specific immunodeficiency, apparently limited to T cell-mediated protection, DTH and its in vitro correlates. Treatment of patients with diffuse cutaneous leishmaniasis using a combination of chemotherapy and combined vaccine immunotherapy (heat-killed promastigotes plus BCG) has induced clinical inactivity and positive DTH in about one third of these patients, accompanied by marked lowering of antibody levels. These results are discussed in terms of Type 1 T cell responses, protective in cell-mediated immune reactions, and Type 2 T cell responses, non-protective in cell-mediated reactions, in the spectrum of leishmaniasis. Factors related to the induction of favorable Type 1 responses to intracellular pathogens are discussed in terms of a possible mechanism of the combined vaccine efficacy and priorities in vaccine development
Asunto(s)
Animales , Humanos , Antígenos de Protozoos/inmunología , Epítopos/inmunología , Leishmaniasis Cutánea/inmunología , Leishmania/inmunología , Anticuerpos Antiprotozoarios/inmunología , Hipersensibilidad Tardía/inmunología , Leishmaniasis Cutánea/terapia , Leishmaniasis Cutánea Difusa/inmunología , Leishmaniasis Mucocutánea/inmunología , Activación de Linfocitos/inmunologíaRESUMEN
Interactions between immunocompetent cells require the participation of T cell antigen receptor (TCR) and the integrin lymphocyte function-associated molecule-1 (LFA-1, CD11a/CD18). These interactions are mediated by interlinking cytokines, which are important in determining the type of immune response. In the present study, we have shown that in American cutaneous leishmaniasis (ACL) lesions, most infiltrating T cells expressed the alpha beta TCR including those selectively migrating to the epidermis. In contrast, gamma delta T cells were abundant in localized (LCL) and scarce in muco-cutaneous (MCL) and diffuse (DCL) cutaneous leishmaniasis, suggesting a role in effective granulomas. There were differences in the expression of LFA-1 alpha and beta subunits, with most cells expressing LFA-1 beta. The ratio LFA-1 beta/LFA-1 alpha was higher in LCL (11.8:1) than in MCL (3.3:1) and DCL (2.4:1). Similar results were observed in Leishmania mexicana-infected C57BL/6 mice. DCL lesions showed a higher proportion of LFA-1 alpha+ cells than MCL and LCL lesions. A reverse-transcriptase polymerase chain reaction (RT-PCR) analysis of the cytokine profiles showed that most T cells present in the MCL and DCL lesions secrete a mixture of Type 1 and Type 2 cytokine patterns, but in DCL granulomas predominate the Type 2 cytokines. In LCL the cytokine patterns show a preponderance of INF gamma over IL-4, and low levels of IL-5 and IL-10, suggesting a Type 1 cytokine profile
Asunto(s)
Animales , Femenino , Humanos , Ratones , Leishmaniasis Cutánea/inmunología , Linfocinas/biosíntesis , Piel/inmunología , Subgrupos de Linfocitos T/inmunología , Anticuerpos Monoclonales , Moléculas de Adhesión Celular/biosíntesis , Granuloma/inmunología , Leishmaniasis Cutánea Difusa/inmunología , Leishmaniasis Mucocutánea/inmunología , Antígeno-1 Asociado a Función de Linfocito/biosíntesis , Linfocinas/inmunología , Ratones Endogámicos C57BL , Reacción en Cadena de la Polimerasa , Receptores de Antígenos de Linfocitos T/biosíntesis , ADN Polimerasa Dirigida por ARN , Linfocitos T/inmunologíaRESUMEN
American mucocutaneous leishmaniasis is a granulomatous disease clinically characterized by ulcerated skin lesions that can regress spontaneously. A small percentage of the affected individuals can however develop a severe destruction of the nasal, oral, pharyngeal and/or laryngeal mucous membranes many years after the healing of the primary lesion. The human immune response to the infection and the possible mechanisms underlying the pathogenesis of the disease, determining either the self-healing or the development of chronic and destructive mucosal lesions, are discussed
Asunto(s)
Citocininas/inmunología , Leishmaniasis Mucocutánea/inmunología , Linfocitos T/inmunologíaRESUMEN
No transcurso de um periodo de 5 anos foram estudados 3 isolados de um paciente com leishmaniose mucosa recidivante causada pela Leishmania (Viannia) braziliensis e 7 clones de um desses isolados. Este estudo foi feito pela analise dos serodemas e zimodemas. Os resultados indicaram a ocorrencia de variacoes fenotipicas clonais. Oito marcadores isoenzimaticos demonstraram diferencas nos padroes eletroforeticos em Acetato de Celulose (AC), bem como em camada fina de amido. Da mesma forma foram constatadas diferencas em um painel de anticorpos monoclonais especificos e subespecificos. Nossas observacoes indicam ainda que a leishmania (Viannia) braziliensis esta composta por subpopulacoes de parasitas com caracteristicas bioquimicas e antigenicas peculiares.