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以及模拟肽作为利什曼病预防潜在抗原候选物的评估。

and Evaluation of Mimetic Peptides as Potential Antigen Candidates for Prophylaxis of Leishmaniosis.

作者信息

Guedes Deborah Carbonera, Santiani Manuel Hospinal, Carvalho Joyce, Soccol Carlos Ricardo, Minozzo João Carlos, Machado de Ávila Ricardo Andrez, de Moura Juliana Ferreira, Ramos Eliezer Lucas Pires, Castro Guillermo Raul, Chávez-Olórtegi Carlos, Thomaz-Soccol Vanete

机构信息

Programa de Pós-Graduação Strictu Sensu em Engenharia de Bioprocessos e Biotecnologia, Universidade Federal do Paraná, Curitiba, Brazil.

Centro de Produção e Pesquisa de Imunobilógicos, Secretaria De Saúde do Estado do Paraná, Piraquara, Brazil.

出版信息

Front Chem. 2021 Jan 15;8:601409. doi: 10.3389/fchem.2020.601409. eCollection 2020.

Abstract

Antigen formulation is the main feature for the success of leishmaniosis diagnosis and vaccination, since the disease is caused by different parasite species that display particularities which determine their pathogenicity and virulence. It is desirable that the antigens are recognized by different antibodies and are immunogenic for almost all species. To overcome this problem, we selected six potentially immunogenic peptides derived from histones and parasite membrane molecules obtained by phage display or spot synthesis and entrapped in liposome structures. We used these peptides to immunize New Zealand rabbits and determine the immunogenic capacity of the chimeric antigen. The peptides induced the production of antibodies as a humoral immune response against or . Next, to evaluate the innate response to induce cellular activation, macrophages from the peptide mix-immunized rabbits were infected with or . The peptide mix generated the IFN-γ, IL-12, IL-4 and TGF-β that led to Th1 and Th2 cellular immune responses. Interestingly, this mix of peptides also induced high expression of iNOS. These results suggest that the mix of peptides derived from histone and parasites membrane molecules was able to mimic parasites proteins and induce cytokines important to CD4+ T cell Th1 and Th2 differentiation and effector molecule to control the parasite infection. Finally, this peptide induced an immune balance that is important to prevent immunopathological disorders, inflammatory reactions, and control the parasite infection.

摘要

抗原制剂是利什曼病诊断和疫苗接种成功的主要特征,因为该疾病由不同的寄生虫物种引起,这些物种具有决定其致病性和毒力的特殊性。理想的情况是,抗原能被不同的抗体识别,并且对几乎所有物种都具有免疫原性。为了克服这个问题,我们选择了六种潜在的免疫原性肽,它们来源于通过噬菌体展示或斑点合成获得的组蛋白和寄生虫膜分子,并包裹在脂质体结构中。我们用这些肽免疫新西兰兔,并确定嵌合抗原的免疫原性能力。这些肽诱导产生抗体,作为针对……或……的体液免疫反应。接下来,为了评估诱导细胞活化的先天反应,将来自肽混合免疫兔的巨噬细胞用……或……感染。肽混合物产生了导致Th1和Th2细胞免疫反应的IFN-γ、IL-12、IL-4和TGF-β。有趣的是,这种肽混合物还诱导了iNOS的高表达。这些结果表明,源自组蛋白和寄生虫膜分子的肽混合物能够模拟寄生虫蛋白,并诱导对CD4+T细胞Th1和Th2分化以及控制寄生虫感染的效应分子很重要的细胞因子。最后,这种肽诱导了一种免疫平衡,这对于预防免疫病理障碍、炎症反应以及控制寄生虫感染很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d1b/7843434/3f996c0ae02c/fchem-08-601409-g0001.jpg

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