leishmania braziliensis
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2021 ◽  
Author(s):  
Camila M. Clemente ◽  
Tatiana Pineda ◽  
Lina M. Yepes ◽  
Yulieth Upegui ◽  
Daniel A. Allemandi ◽  
...  

2021 ◽  
Author(s):  
Maria Gabriella Nunes de Melo ◽  
Isabelle Barreto da Silva Moreira Reino ◽  
Victor Vaitkevicius Antão de Souza Souza ◽  
Jady Moreira da Silva ◽  
Rayana Carla Silva De Morais ◽  
...  

Introdução: O regime terapêutico utilizado no tratamento da Leishmaniose Tegumentar Americana (LTA) é direcionado apenas para morte do parasito, não exerce influência sobre a resposta imune do hospedeiro (1, 2). Desta forma, é essencial desenvolver novos alvos terapêuticos que possam estabelecer uma modulação entre os perfis Th1 (inflamação/proteção) e Th2 (suscetibilidade a infecção), para uma futura cura clínica (3). Estudos com produtos naturais, como a microalga Chlorella vulgaris (CV), estão sendo considerados promissores por apresentarem potencial para atividades terapêuticas e antiparasitárias (4, 5), com facilidade e baixo custo de produção. Objetivo: Assim, o objetivo deste estudo é avaliar in vitro o preliminar potencial terapêutico da C. vulgaris pela obtenção do Índice de Seletividade (IS). Métodos: O extrato de CV foi obtido após cultivo, por sonicação. Para obtenção do IS, utilizou-se Células Mononucleares do Sangue Periférico (PBMC) de humanos, para a determinação da Concentração Citotóxica de 50% (CC50), pelo método de MTT, e ensaios de concentração inibitória de 50% (IC50), em células promastigotas de Leishmania braziliensis, através de contagem celular por microscopia óptica. Ambos os ensaios foram tratados com o extrato de CV e as drogas de referência (DR) (antimoniato pentavalente [SbV] e miltefosina), em concentrações seriadas entre 1000μg/mL e 62,5μg/mL para a CC50, entre 500μg/mL e 0,1 μg/mL para a IC50. O valor de IS foi determinado pela razão entre a CC50 e IC50. Resultados: Para os ensaios de CC50 em PBMC humano, verificou-se baixa toxidade demostrada pela elevada viabilidade celular com o extrato de CV (999,66μg/ml), quando comparado com as DR (SbV= 412,46μg/ml e Miltefosina=159,49μg/ml). Além disso, a IC50 do extrato de CV (144,93μg/ml) apresentou baixa toxicidade para a L. braziliensis, com dados próximos ao do Sbv (119,76μg/ml), mas a Miltefosina (IC50=1,02μg/mL) apresentou uma maior atividade leishmanicida, porém foi o mais tóxico para células humanas. O IS do extrato de CV (IS=6,9) obteve resultado superior ao do Sbv(IS=3,44), apresentando maior seletividade contra o parasito e menor toxidade para as células humanas, e a miltefosina possui o maior valor, sendo 100 vezes mais seletivo para o parasito. Conclusões: Portanto, com base nos dados obtidos o extrato de CV, não tóxico para células humanas e seletivo contra o parasito, possui potencial para futuros estudos in vivo com base no desenvolvimento de novas terapias contra LTA.


2021 ◽  
Vol 1 (8) ◽  
pp. A246
Author(s):  
Camille Wagner ◽  
Guillaume Gregorowicz ◽  
Alison Blind ◽  
Charlotte Klein ◽  
Carine Merklen ◽  
...  

Author(s):  
Maira Alemán Santos ◽  
Lina Martínez-Pérez ◽  
Matilde Rivero-Rodríguez ◽  
Luis Cortés-Alemán ◽  
Alveiro Pérez-Doria ◽  
...  

Introducción: Aunque la leishmaniasis visceral (LV) es endémica en el Caribe colombiano, en los últimos años se ha observado un incremento en su área de distribución, con el registro de casos en nuevas localidades. Objetivos: En este estudio se caracterizaron los flebotomíneos, parásitos del género Leishmania y algunos vertebrados domésticos asociados al primer caso humano de LV en la vereda Toro, San Juan Nepomuceno, Bolívar, Colombia. Metodología: Los insectos fueron sometidos a extracción, amplificación y secuenciación de ADN para establecer si estaban infectados con Leishmania spp. e identificar sus ingestas sanguíneas. Adicionalmente, en los caninos se determinaron los títulos de anticuerpos anti-Leishmania mediante la técnica de inmunofluorescencia indirecta. Resultados: En total se recolectaron 2178 flebotomíneos, el 99,6% de los cuales fue identificado como Lutzomyia evansi. Los parásitos Leishmania infantum y Leishmania braziliensis fueron detectados en esta especie, con una frecuencia mínima de infección de 0,003% (3/1070) y 0,0009% (1/1070), respectivamente. El 16,73% de las hembras de Lu. evansi se encontraron alimentadas de Homo sapiens sapiens, el 16,32% de  Capra hircus , el 12,45% de Sus scrofa domesticus, el 11,63 % de Bos indicus y el 9,79% de Canis familiaris. Uno de ocho caninos serológicamente evaluados fue positivo para leishmaniasis canina. Conclusión: El hallazgo en Lu. evansi de ingestas de sangre mixtas de humanos y caninos, evidencia el vínculo epidemiológico entre las Lutzomyia infectados con el parásito, los potenciales reservorios y la población humana, lo que explicaría la aparición del primer caso de LV en esta localidad del Caribe colombiano.


Author(s):  
Daniel Holanda Barroso ◽  
Otávio de Toledo Nóbrega ◽  
Carla Nunes de Araújo ◽  
Gustavo Subtil Magalhães Freire ◽  
Sofia Sales Martins ◽  
...  

Leishmania braziliensis is the most important causal agent of American tegumentary leishmaniasis (ATL), and 3 to 5% of patients develop mucosal lesions. The mechanisms related to parasite and host immune interactions and the parasite life cycle that lead to dissemination to the mucosa are poorly understood. We aimed to detect L. braziliensis DNA in the nasal mucosa of cutaneous leishmaniasis (CL) patients with early mucous dissemination and to relate those findings to specific inflammatory responses. Nasal swabs were collected from patients with the cutaneous form of ATL. L. braziliensis DNA was investigated using TaqMan-based real-time PCR. The levels of serum cytokines (IL-12, IL-6, TNF-α, IL-10, IL-1β and IL-8) were measured by a multiplex cytometric array. A Poisson regression model was used to test prevalence ratios (PRs) and multivariate interactions of clinical and laboratory characteristics. Of the 79 CL patients, 24 (30%) had L. braziliensis DNA in the nasal mucosa. In the multivariate model, parasite DNA presence in mucosa was associated with a reduction in IL-12 levels (PR = 0.440; p=0.034), increased IL-6 levels (PR = 1.001; p=0.002) and a higher number of affected body segments (PR = 1.65; p<0.001). In this study, we observed a higher rate of early dissemination to the nasal mucosa than what was previously described. We suggest that an enhanced Th1 profile characterized by higher IL-12 is important for preventing dissemination of L. braziliensis to the mucosa. Further evaluation of parasite-related interactions with the host immunological response is necessary to elucidate the dissemination mechanisms of Leishmania.


2021 ◽  
Vol 12 (4) ◽  
pp. 765-778
Author(s):  
Sara Nunes ◽  
Mariana Rosa Ampuero ◽  
Ícaro Bonyek-Silva ◽  
Reinan Lima ◽  
Filipe Rocha Lima ◽  
...  

Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) amplifies the immune response, operating synergistically with Toll-Like Receptors (TLRs) in the production of inflammatory mediators. TREM-1 signaling depends on the adapter protein DAP12, which results in the activation of NFkB, the expression of inflammatory genes, and the release of antimicrobial peptides, such as Beta-defensin 2. We evaluated the activation of the TREM-1 signaling pathways in Cutaneous Leishmaniasis (CL) caused by Leishmania braziliensis and linage human keratinocytes exposed to these parasites since the host immune response against Leishmania plays a critical role in promoting parasite killing but also participates in inflammation and tissue damage. We analyzed publicly available transcriptome data from the lesions of CL patients. In the CL biopsies, we found increased expression of the molecules involved in the TREM-1 pathway. We then validated these findings with RT-qPCR and immunohistochemistry in newly obtained biopsies. Surprisingly, we found a strong labeling of TREM-1 in keratinocytes, prompting the hypothesis that increased TREM-1 activation may be the result of tissue damage. However, increased TREM-1 expression was only seen in human lineage keratinocytes following parasite stimulation. Moreover, no up-regulation of TREM-1 expression was observed in the skin lesions caused by other non-infectious inflammatory diseases. Together, these findings indicate that L. braziliensis (Lb) induces the expression of the TREM-1 receptor in tissue keratinocytes regardless of tissue damage, suggesting that non-immune skin cells may play a role in the inflammatory response of CL.


2021 ◽  
Vol 12 ◽  
Author(s):  
Pedro Paulo Carneiro ◽  
Andreza S. Dórea ◽  
Walker N. Oliveira ◽  
Luiz Henrique Guimarães ◽  
Claúdia Brodskyn ◽  
...  

Human cutaneous leishmaniasis (CL) caused by Leishmania braziliensis is characterized by a pronounced inflammatory response associated with ulcer development. Monocytes/macrophages, the main cells harboring parasites, are largely responsible for parasite control. Toll-like receptor (TLR) signaling leads to the transcription of inflammatory mediators, such as IL-1β and TNF during innate immune response. TLR antagonists have been used in the treatment of inflammatory disease. The neutralization of these receptors may attenuate an exacerbated inflammatory response. We evaluated the ability of TLR2 and TLR4 antagonists to modulate host immune response in L. braziliensis-infected monocytes and cells from CL patient skin lesions. Following TLR2 and TLR4 neutralization, decreased numbers of infected cells and internalized parasites were detected in CL patient monocytes. In addition, reductions in oxidative burst, IL-1β, TNF and CXCL9 production were observed. TNF production by cells from CL lesions also decreased after TLR2 and TLR4 neutralization. The attenuation of host inflammatory response after neutralizing these receptors suggests the potential of TLR antagonists as immunomodulators in association with antimonial therapy in human cutaneous leishmaniasis.


Acta Tropica ◽  
2021 ◽  
pp. 106182
Author(s):  
Jair Téllez ◽  
Alejandra Amarillo ◽  
Carolina Suarez ◽  
Carlos Cardozo ◽  
Diego Guerra ◽  
...  

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Manon Geerts ◽  
Achim Schnaufer ◽  
Frederik Van den Broeck

Abstract Background The advent of population-scale genome projects has revolutionized our biological understanding of parasitic protozoa. However, while hundreds to thousands of nuclear genomes of parasitic protozoa have been generated and analyzed, information about the diversity, structure and evolution of their mitochondrial genomes remains fragmentary, mainly because of their extraordinary complexity. Indeed, unicellular flagellates of the order Kinetoplastida contain structurally the most complex mitochondrial genome of all eukaryotes, organized as a giant network of homogeneous maxicircles and heterogeneous minicircles. We recently developed KOMICS, an analysis toolkit that automates the assembly and circularization of the mitochondrial genomes of Kinetoplastid parasites. While this tool overcomes the limitation of extracting mitochondrial assemblies from Next-Generation Sequencing datasets, interpreting and visualizing the genetic (dis)similarity within and between samples remains a time-consuming process. Results Here, we present a new analysis toolkit—rKOMICS—to streamline the analyses of minicircle sequence diversity in population-scale genome projects. rKOMICS is a user-friendly R package that has simple installation requirements and that is applicable to all 27 trypanosomatid genera. Once minicircle sequence alignments are generated, rKOMICS allows to examine, summarize and visualize minicircle sequence diversity within and between samples through the analyses of minicircle sequence clusters. We showcase the functionalities of the (r)KOMICS tool suite using a whole-genome sequencing dataset from a recently published study on the history of diversification of the Leishmania braziliensis species complex in Peru. Analyses of population diversity and structure highlighted differences in minicircle sequence richness and composition between Leishmania subspecies, and between subpopulations within subspecies. Conclusion The rKOMICS package establishes a critical framework to manipulate, explore and extract biologically relevant information from mitochondrial minicircle assemblies in tens to hundreds of samples simultaneously and efficiently. This should facilitate research that aims to develop new molecular markers for identifying species-specific minicircles, or to study the ancestry of parasites for complementary insights into their evolutionary history.


2021 ◽  
Author(s):  
Lucas Lorenzon ◽  
Jose Carlos Quilles ◽  
Gustavo Daniel Campagnaro ◽  
Leticia Almeida ◽  
Flavio Protasio Veras ◽  
...  

In trypanosomatids, regulation of gene expression occurs mainly at the posttranscriptional level, and RNA-binding proteins (RBPs) are key players in determining the fates of transcripts. RBPs are major targets of protein arginine methyltransferases (PRMTs), which posttranslationally regulate the RNA-binding capacity and other macromolecular interactions of RBPs by transferring methyl groups to protein arginine residues. Herein, we present the results of a study that functionally characterized the five predicted PRMTs in Leishmania braziliensis by gene knockout and endogenous protein HA tagging using CRISPR/Cas9 gene editing. We report that arginine methylation profiles vary among Leishmania species and that target protein methylation changes across different L. braziliensis life cycle stages, with higher PRMT expression in the promastigote stages than in the axenic amastigote stage. Knockout of some of the L. braziliensis PRMTs led to significant changes in global arginine methylation patterns without affecting promastigote axenic growth. Deletion of either PRMT1 or PRMT3 disrupted most type I PRMT activity, resulting in a global increase in monomethyl arginine (MMA) levels, which is mainly catalyzed by PRMT7. Putative targets and/or PRMT-interacting proteins were identified by coimmunoprecipitation using HA-tagged PRMTs, revealing a network of target RBPs and suggesting functional interactions between them and a relevant participation in epigenetic control of gene expression. Finally, we demonstrate that L. braziliensis PRMT1 and PRMT5 are required for efficient macrophage infection in vitro, and that in the absence of PRMT1 and PRMT5, axenic amastigote proliferation is impaired. The results indicate that arginine methylation is modulated across life cycle stages in L. braziliensis and show possible functional overlap and cooperation among the different PRMTs in targeting proteins. Overall, our data suggest important regulatory roles of these proteins throughout the L. braziliensis life cycle, showing that arginine methylation is important for parasite-host cell interactions.


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