scholarly journals PARTICIPAÇÃO DOS RECEPTORES TOLL-LIKE NA RESPOSTA A INFECÇÃO in vitro POR Leishmania (Viannia) braziliensis: UMA REVISÃO DE LITERATURA

2021 ◽  
Vol 2 (1) ◽  
pp. 54
Author(s):  
Anna Clara Silva Fonseca ◽  
Nathália Brígida de Oliveira ◽  
Daniela Camargos Costa
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Natural Killer ◽  
Leishmania Braziliensis ◽  
Toll Like Receptors ◽  
American Cutaneous Leishmaniasis ◽  
Tnf Α ◽  
Mucosal Leishmaniasis

Introdução: A Leishmania braziliensis é um protozoário da família Trypanosomatidae responsável pelo desenvolvimento de uma das formas dermotrópicas da doença denominada leishmaniose mucosa (LM). O parasito é intracelular obrigatório e se multiplica dentro dos macrófagos e monócitos de seus hospedeiros. Os receptores tolllike (TLR) são glicoproteínas transmembrana presentes nas células de defesa, principalmente Natural Killer, macrófagos e células dendríticas, que reconhecem estruturas microbianas e que promovem uma série de sinais que produzem citocinas próinflamatórias importantes para que a resposta imune inata seja efetiva, como por exemplo TNF-α, IL-10 e TGF-β. Objetivo: Realizar revisão da literatura a respeito do papel dos receptores Toll-like na resposta à infecção in vitro por L. braziliensis. Material e métodos: Realizado no formato de revisão integrativa, a pesquisa abrangeu artigos científicos das bases de dados SCIELO e PUBMED. Os descritores utilizados foram “American Cutaneous leishmaniasis”, “Leishmania braziliensis”, “mucosal leishmaniasis” e “Toll-like receptors”. Foram selecionados artigos acadêmicos originais, escritos na língua inglesa, que foram publicados no período de 2014 a 2020, obtendo -se 20 artigos. Após a leitura dos títulos e resumos e ao adotar os critérios de exclusão, foram selecionados 12 artigos originais para a presente revisão. Resultados: As pesquisas selecionadas avaliaram 147 pacientes com diagnóstico histopatológico de Leishmaniose Cutânea (LC). Os pacientes que apresentavam LM, concomitantemente possuíam uma maior expressão de células TCD4+, TCD8+, IL-10+ e TGF-β+ em comparação com aqueles que possuíam LC, que expressavam uma menor quantidades dessas citocinas. Em oposição, o TNF-α em pacientes com LC, encontrava-se aumentado se comparada a LM. Na análise relacionada a TLR-2 e TLR-4, houve uma maior expressão em monócitos nos pacientes com LC associadas a L. braziliensis e que o bloqueio dos TRL reduziu as respostas oxidativas das células de pacientes com LC. Conclusão: Diante dos resultados é possível concluir que a maior expressão de TLR-2 e TLR-4 promove a hiper-reatividade de citocinas pró-inflamatórias e consequente pré-disposição para desenvolvimento da doença. Portanto, seu bloqueio é eficaz para redução das lesões. Esse dado demonstra a relação e o papel dos TLR na infecção por L. braziliensis, trazendo importantes esclarecimentos para a resposta imune e desenho vacinal.

scholarly journals Granzyme B Produced by Natural Killer Cells Enhances Inflammatory Response and Contributes to the Immunopathology of Cutaneous Leishmaniasis

2019 ◽  
Vol 221 (6) ◽  
pp. 973-982 ◽  
Author(s):  
Taís M Campos ◽  
Fernanda O Novais ◽  
Maíra Saldanha ◽  
Rúbia Costa ◽  
Morgana Lordelo ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Cutaneous Leishmaniasis ◽  
Natural Killer ◽  
Cd8 T Cells ◽  
Granzyme B ◽  
Skin Lesions ◽  
Interferon Γ ◽  
Leishmania Braziliensis

Abstract Background Skin lesions from patients infected with Leishmania braziliensis has been associated with inflammation induced by cytotoxic CD8+ T cells. In addition, CD8+ T cell-mediated cytotoxicity has not been linked to parasite killing. Meanwhile, the cytotoxic role played by natural killer (NK) cells in cutaneous leishmaniasis (CL) remains poorly understood. Methods In this study, we observed higher frequencies of NK cells in the peripheral blood of CL patients compared with healthy subjects, and that NK cells expressed more interferon-γ, tumor necrosis factor (TNF), granzyme B, and perforin than CD8+ T cells. Results We also found that most of the cytotoxic activity in CL lesions was triggered by NK cells, and that the high levels of granzyme B produced in CL lesions was associated with larger lesion size. Furthermore, an in vitro blockade of granzyme B was observed to decrease TNF production. Concclusions Our data, taken together, suggest an important role by NK cells in inducing inflammation in CL, thereby contributing to disease immunopathology.

scholarly journals Effects of Meglumine Antimoniate Treatment on Cytokine Production in a Patient with Mucosal Leishmaniasis and Chagas Diseases Co-Infection

2020 ◽  
Vol 5 (2) ◽  
pp. 69 ◽  
Author(s):  
Karine Rezende-Oliveira ◽  
Cesar Gómez-Hernández ◽  
Marcos Vinícius da Silva ◽  
Rafael Faria de Oliveira ◽  
Juliana Reis Machado ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Mononuclear Cells ◽  
Interleukin 10 ◽  
Treg Cells ◽  
Interleukin 12 ◽  
Leishmania Braziliensis ◽  
T Regulatory Cell ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Mucosal Leishmaniasis

The influence of antimoniate treatment on specific anti-protozoan T-cell responses was evaluated in a 48-year-old male patient diagnosed with mucosal leishmaniasis and Chagas disease infection. Before and after treatment, PBMC (peripheral blood mononuclear cells) were cultured in the absence or presence of Leishmania braziliensis or Trypanosoma cruzi live parasites, their soluble antigens, or PHA (phytohaemagglutinin). Cytokines were measured and Treg (T regulatory) cell percentages were quantified. Before treatment, PBMC were able to produce higher amounts of TNF-α, IL-6 (Interleukin-6), and IL-10 (Interleukin-10) but lower amounts of IL-12 (Interleukin-12) in response to culture stimulation. However, after treatment, there was a down-modulation of TNF-α, IL-6, and IL-10 cytokines but an up-modulation in IL-12 production. PBMC had the ability to produce TNF-α only against live parasites or PHA. There was an overall decrease of circulating Treg cells after treatment. In mixed Leishmaniasis and Chagas disease infection, treatment with antimoniate could modulate immune responses toward a more protective profile to both diseases.

scholarly journals Flow Cytometric Determination of Cellular Sources and Frequencies of Key Cytokine-Producing Lymphocytes Directed against Recombinant LACK and Soluble Leishmania Antigen in Human Cutaneous Leishmaniasis

2001 ◽  
Vol 69 (5) ◽  
pp. 3232-3239 ◽  
Author(s):  
R. L. A. Bottrel ◽  
W. O. Dutra ◽  
F. A. Martins ◽  
B. Gontijo ◽  
E. Carvalho ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cutaneous Leishmaniasis ◽  
Ex Vivo ◽  
Protozoan Parasite ◽  
Recombinant Antigen ◽  
Interleukin 4 ◽  
Leishmania Braziliensis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Leishmaniasis, caused by infection with the protozoan parasiteLeishmania, affects millions of individuals worldwide, causing serious morbidity and mortality. This study directly determined the frequency of cells producing key immunoregulatory cytokines in response to the recombinant antigen Leishmania homolog of receptors for activated kinase C (LACK) and soluble leishmania antigen (SLA), and it determined relative contributions of these antigens to the overall cytokine profile in individuals infected for the first time with Leishmania braziliensis. All individuals presented with the cutaneous clinical form of leishmaniasis and were analyzed for proliferative responses to LACK antigen and SLA, frequency of lymphocyte subpopulations (analyzed ex vivo), and antigen-induced (LACK and SLA) cytokine production at the single-cell level (determined by flow cytometry). The following were determined. (i) The Th1-type response previously seen in patients with cutaneous leishmaniasis is due to gamma interferon (IFN-γ) production by several different sources, listed in order of contribution: CD4+ T lymphocytes, CD4−, CD8− lymphocytes, and CD8+ T lymphocytes. (ii) SLA induced a higher frequency of lymphocytes producing IFN-γ and tumor necrosis factor alpha (TNF-α) than did LACK. (iii) LACK induced an activation of monocyte populations as reflected by an increased percentage of CD14-positive cells. (iv) Neither SLA nor LACK induced detectable frequencies of cells producing interleukin-4 (IL-4) or IL-5. These data demonstrated a multifaceted immune response to SLA in human leishmaniasis involving Th1 CD4+ T lymphocytes (IFN-γ+ and IL-10−/IL-4−), Tc1 CD8+ T cells (IFN-γ+, and IL-10−/IL-4−), and a high frequency of TNF-α-producing lymphocytes. Moreover, it was determined that the recombinant antigen LACK acts as a weak inducer of Th1-type lymphocyte responses compared to SLA.

In vitro infectivity of species of Leishmania (Viannia) responsible for American cutaneous leishmaniasis

2008 ◽  
Vol 103 (4) ◽  
pp. 771-776 ◽  
Author(s):  
Marliane Batista Campos ◽  
Cláudia Maria De Castro Gomes ◽  
Adelson Alcimar Almeida de Souza ◽  
Ralph Lainson ◽  
Carlos Eduardo Pereira Corbett ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
American Cutaneous Leishmaniasis

scholarly journals Analysis of the specificity of human antibodies to antigens of Leishmania braziliensis braziliensis

1989 ◽  
Vol 31 (4) ◽  
pp. 228-234 ◽  
Author(s):  
Aoi Masuda ◽  
Sueli Fátima do Nascimento ◽  
Carmem Silvia Guerra ◽  
Gláucia da Silva Paranhos ◽  
Antonio Walter Ferreira
Keyword(s):  
Visceral Leishmaniasis ◽  
Cutaneous Leishmaniasis ◽  
Chagas Disease ◽  
The Other ◽  
Leishmania Braziliensis ◽  
Human Antibodies ◽  
American Cutaneous Leishmaniasis

The antigenicity of promastigotes of Leishmania braziliensis braziliensis (L. b.braziliensis) treated with 1% sodium desoxycholate in 10 mM Tris-Hcl pH 8.2 was analysed by immunoblot using as probes sera from American cutaneous leishmaniasis (ACL), American visceral leishmaniasis (AVL), schistosomiasis, malaria and Chagas' disease. The ACL sera reacted constantly with a 60 kD band. No reactivity to this protein was observed with sera from the other diseases above mentioned indicating that the 60 kD protein may be used in serodiagnosis for ACL.

scholarly journals Study of an outbreak of cutaneous leishmaniasis in Venezuela: the role of domestic animals

1984 ◽  
Vol 79 (2) ◽  
pp. 181-195 ◽  
Author(s):  
Cruz Manuel Aguilar ◽  
Elio Fernandez ◽  
Reina de Fernandez ◽  
Leonidas M. Deane
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Domestic Animals ◽  
Small Sample ◽  
The Other ◽  
Leishmania Braziliensis ◽  
Wild Mammals ◽  
American Cutaneous Leishmaniasis ◽  
Equus Asinus ◽  
Sources Of Infection

During an outbreak of cutaneous leishmaniasis in a locality (Las Rosas, Cojedes State, venezuela) previously non-endemic, 12.9% of humans, 7% of dogs and 21.4% of donkeys (Equus asinus) had lesions with paraites. The agent in the three hosts was identified as Leishmania braziliensis, subspecies braziliensis at least in man and donkey. The probable vector was Lutzomyia panamensis. No infection was found in a small sample of wild mammals examined. The outbreak was apparently linked with the importation of donkeys with ulcers, from endemic areas. The Authors call attention to the fact that not only in the foci of "uta", but also in areas of the other forms of American cutaneous leishmaniasis, dogs are frequently found infected. They emphasize the necessity of searching for the infection in donkeys and of performing hemocultures and xenodiagnosis with sandflies in human, canine and equine cases, to verify their possible role as sources of infection, and not merely as dead ends in the epidemiological chain of the disease.

scholarly journals Exploring Antiparasitic Molecule Sources from Timber by-Product Industries—Leishmanicidal and Trypanocidal Compounds from Clathrotropis brunnea Amshoff

2020 ◽  
Vol 11 ◽  
Author(s):  
Fernando Torres ◽  
Sara M. Robledo ◽  
Wiston Quiñones ◽  
Gustavo Escobar ◽  
Rosendo Archbold ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Ethanol Extract ◽  
Leishmania Braziliensis ◽  
Moderate Activity ◽  
Hamster Model ◽  
Cutaneous Ulcer ◽  
Pure Substances ◽  
Pharmacological Potential ◽  
Median Effective Concentration

Through bioguided in vitro assays, the leishmanicidal and trypanocidal effects of an ethanol extract, seven fractions, and two pure substances obtained from Clathrotropis brunnea Amshoff sawdust were established. The effectiveness of the two metabolites was confirmed in a hamster model of cutaneous Leishmaniasis by Leishmania braziliensis and in Balb/c mice infected by Trypanosoma cruzi. In vitro, 3,5-dimethoxystilbene was the most active against L. braziliensis amastigotes, with a median lethal concentration (LC50) of 4.18 μg/ml (17.40 μM) and a selectivity index of 3.55, but showed moderate activity for T. cruzi, with a median effective concentration (EC50) value of 27.7 μg/ml (115.36 μM). Flavanone pinostrobin, meanwhile, showed high activity against L. braziliensis, with an EC50 of 13.61 μg/ml (50.39 μM), as well as for T. cruzi, with an EC50 of 18.2 μg/ml (67.38 μM). The animal model assay of cutaneous Leishmaniasis showed that 50% of the hamsters treated with pinostrobin were definitively cured the cutaneous ulcer, and 40% showed an improvement, with a reduction in the size of the of 84–87%. Moreover, Balb/c mice experimentally infected with T. cruzi and treated for 25 days with pinostrobin experienced a reduction in their parasitemia by 71%. These results demonstrate the high potential of C. brunnea Amshoff against cutaneous Leishmaniasis and American trypanosomiasis and indicate the pharmacological potential of waste from the wood industry, which has tons of potentially useful chemicals for the development of new medicines.

American Leishmania spp: Formycin B treatment of cutaneous leishmaniasis in mice

Parasitology ◽  
1987 ◽  
Vol 94 (3) ◽  
pp. 467-474 ◽  
Author(s):  
Tamara Rojas ◽  
J. L. Avila
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Optimal Dose ◽  
Dose Schedule ◽  
Inhibitory Effect ◽  
American Cutaneous Leishmaniasis ◽  
Leishmania Spp ◽  
Low Toxicity ◽  
Foot Pad

Using foot-pad infection of female C57BL/6, DBA/2J and NMRI-IVIC mice as an animal model for American cutaneous leishmaniasis (ACL), we evaluated the inhibitory effect of Formycin B (FoB) on the infection produced by 7 different Leishmania isolates. When treatment was initiated some days, or even some weeks, after infection a significant leishmanistatic effect was detected on mice infected with all Leishmania isolates, which reached 30–55 weeks for some isolates. The optimal dose schedule was 1·25 mg/kg body weight/day, injected intraperitoneally for 20 consecutive days. Significant differences in the sensitivity of various Leishmania spp. to FoB were found, either in vivo, or in vitro where a high [3H]FoB incorporation rate was found only for certain Leishmania isolates. The low toxicity of this drug and the sensitivity of the 7 Leishmania isolates tested suggest that FoB could be useful in the treatment of ACL.

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