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在实验性克氏锥虫感染过程中作为抗原的磷脂和磷脂酶A1

Phospholipids and phospholipase A1 as antigens during the course of experimental Trypanosoma cruzi infection.

作者信息

Bott Emanuel, López Sebastián Andrés, Gimenez Guadalupe, Solana María Elisa, Belaunzarán María Laura

机构信息

Universidad de Buenos Aires, Facultad de Medicina, Departamento de Microbiología, Parasitología e Inmunología, Buenos Aires, Argentina.

Consejo Nacional de Investigaciones Científicas y Técnicas-CONICET, Universidad de Buenos Aires, Instituto de Investigaciones en Microbiología y Parasitología Médica, Buenos Aires, Argentina.

出版信息

Mem Inst Oswaldo Cruz. 2025 Sep 15;120:e240281. doi: 10.1590/0074-02760240281. eCollection 2025.

Abstract

BACKGROUND

Trypanosoma cruzi, causative agent of Chagas disease (CD), remains a public health problem in Latin America and is emerging in non-endemic areas. Phospholipids (PL) are essential components of biomembranes and their enzymatic modification by phospholipases yields bioactive lipids that modulate immune responses. Anti-PL antibodies have been associated with autoimmune diseases and inflammation, potentially influencing CD pathology by recognising PL and PL-binding proteins. T. cruzi Phospholipase A1 (TcPLA1) hydrolyses membrane PL and participates in parasite-host cell interactions.

OBJECTIVES

This study evaluated IgM and IgG antibody responses against phosphatidylcholine, phosphatidylethanolamine, and their derived lysophospholipids (LPL), as well as recombinant TcPLA1, during experimental T. cruzi infection with two strains: RA (high virulence) and K98 (low virulence). It also aimed to predict the recognition capacity of TcPLA1 by CD patients using in silico analysis.

METHODS

Antibody responses were analysed by enzyme-linked immunosorbent assay (ELISA) using different PL and recombinant TcPLA1 as antigens. Lytic activity assays were performed to evaluate the functional impact of anti-PL antibodies. The CHAGASTOPE resource was used to predict TcPLA1 antigenicity.

FINDINGS

This study identified IgM and IgG antibodies against PL, LPL and TcPLA1 during experimental T. cruzi infection. Different amino acid sequences of TcPLA1 showed stronger antigenic recognition by CD patient's sera.

MAIN CONCLUSIONS

The presence of these antibodies suggests their involvement in the pathogenesis of CD and their potential as markers for disease monitoring and prognosis.

摘要

背景

克氏锥虫是恰加斯病(CD)的病原体,在拉丁美洲仍是一个公共卫生问题,并且正在非流行地区出现。磷脂(PL)是生物膜的重要组成部分,它们被磷脂酶进行酶促修饰会产生调节免疫反应的生物活性脂质。抗磷脂抗体与自身免疫性疾病和炎症有关,可能通过识别磷脂和磷脂结合蛋白影响恰加斯病的病理过程。克氏锥虫磷脂酶A1(TcPLA1)可水解膜磷脂并参与寄生虫与宿主细胞的相互作用。

目的

本研究评估了在实验性克氏锥虫感染两种菌株(RA,高毒力;K98,低毒力)期间,针对磷脂酰胆碱、磷脂酰乙醇胺及其衍生的溶血磷脂(LPL)以及重组TcPLA1的IgM和IgG抗体反应。它还旨在通过计算机分析预测恰加斯病患者对TcPLA1的识别能力。

方法

使用不同的磷脂和重组TcPLA1作为抗原,通过酶联免疫吸附测定(ELISA)分析抗体反应。进行溶血活性测定以评估抗磷脂抗体的功能影响。利用CHAGASTOPE资源预测TcPLA1的抗原性。

研究结果

本研究在实验性克氏锥虫感染期间鉴定出了针对磷脂、溶血磷脂和TcPLA1的IgM和IgG抗体。TcPLA1的不同氨基酸序列显示出被恰加斯病患者血清更强的抗原识别。

主要结论

这些抗体的存在表明它们参与恰加斯病的发病机制,以及作为疾病监测和预后标志物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a9c/12440295/96a828b32c15/1678-8060-mioc-120-e240281-gf1.jpg

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