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牛型分枝杆菌卡介苗菌株 Moreau 和 Pasteur 对细胞内巨噬细胞环境反应的差异。

Differences in responses to the intracellular macrophage environment between Mycobacterium bovis BCG vaccine strains Moreau and Pasteur.

机构信息

Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Genômica Funcional e Bioinformática, Rio de Janeiro, RJ, Brasil.

Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Molecular de Insetos, Rio de Janeiro, RJ, Brasil.

出版信息

Mem Inst Oswaldo Cruz. 2023 Oct 13;118:e230070. doi: 10.1590/0074-02760230070. eCollection 2023.

DOI:10.1590/0074-02760230070
PMID:37851722
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10581373/
Abstract

BACKGROUND

The Bacille Calmette-Guérin (BCG) vaccine comprises a family of strains with variable protective efficacy against pulmonary tuberculosis (TB) and leprosy, partly due to genetic differences between strains.

OBJECTIVES

Previous data highlighting differences between the genomes and proteomic profiles of BCG strains Moreau and Pasteur led us to evaluate their behaviour in the macrophage microenvironment, capable of stimulating molecular responses that can impact the protective effect of the vaccine.

METHODS

Strain infectivity, viability, co-localisation with acidified vesicles, macrophage secretion of IL-1 and MCP-1 and lipid droplet biogenesis were evaluated after infection.

FINDINGS

We found that BCG Moreau is internalised more efficiently, with significantly better intracellular survival up to 96 h p.i., whereas more BCG Pasteur bacilli were found co-localised in acidified vesicles up to 6 h p.i. IL-1β and MCP-1 secretion and lipid droplet biogenesis by infected macrophages were more prominent in response to BCG Pasteur.

MAIN CONCLUSION

Overall, our results show that, compared to Pasteur, BCG Moreau has increased fitness and better endurance in the harsh intracellular environment, also regulating anti-microbial responses (lower IL-1b and MCP-1). These findings contribute to the understanding of the physiology of BCG Moreau and Pasteur in response to the intraphagosomal environment in a THP-1 macrophage model.

摘要

背景

卡介苗（BCG）疫苗由一系列菌株组成，这些菌株对肺结核（TB）和麻风病的保护效力存在差异，部分原因是菌株之间存在遗传差异。

目的

先前的数据强调了卡介苗菌株莫罗和巴斯德之间基因组和蛋白质组图谱的差异，这促使我们评估它们在巨噬细胞微环境中的行为，因为巨噬细胞微环境能够刺激分子反应，从而影响疫苗的保护效果。

方法

在感染后评估了菌株感染性、生存能力、与酸化小泡的共定位、巨噬细胞分泌的白细胞介素-1 和单核细胞趋化蛋白-1 以及脂滴生物发生的情况。

结果

我们发现卡介苗莫罗的内化效率更高，在 96 小时内的细胞内存活率明显更好，而在感染 6 小时内，更多的卡介苗巴斯德杆菌被发现与酸化小泡共定位。受感染的巨噬细胞分泌白细胞介素-1β和单核细胞趋化蛋白-1 以及脂滴生物发生的情况对卡介苗巴斯德的反应更为明显。

主要结论

总体而言，与巴斯德相比，与巴斯德相比，卡介苗莫罗在恶劣的细胞内环境中具有更高的适应性和更好的耐力，还能调节抗微生物反应（较低的白细胞介素-1b 和单核细胞趋化蛋白-1）。这些发现有助于理解卡介苗莫罗和巴斯德在 THP-1 巨噬细胞模型中对吞噬体内环境的生理反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0103/10581373/5fb6867af982/1678-8060-mioc-118-e230070-gf7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0103/10581373/2c1ea9e8216d/1678-8060-mioc-118-e230070-gf1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0103/10581373/b25e001d1b29/1678-8060-mioc-118-e230070-gf2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0103/10581373/cc817235d212/1678-8060-mioc-118-e230070-gf3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0103/10581373/2d0028264e9d/1678-8060-mioc-118-e230070-gf4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0103/10581373/d94f92ba001e/1678-8060-mioc-118-e230070-gf5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0103/10581373/36f5f5c2bea7/1678-8060-mioc-118-e230070-gf6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0103/10581373/5fb6867af982/1678-8060-mioc-118-e230070-gf7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0103/10581373/2c1ea9e8216d/1678-8060-mioc-118-e230070-gf1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0103/10581373/b25e001d1b29/1678-8060-mioc-118-e230070-gf2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0103/10581373/cc817235d212/1678-8060-mioc-118-e230070-gf3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0103/10581373/2d0028264e9d/1678-8060-mioc-118-e230070-gf4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0103/10581373/d94f92ba001e/1678-8060-mioc-118-e230070-gf5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0103/10581373/36f5f5c2bea7/1678-8060-mioc-118-e230070-gf6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0103/10581373/5fb6867af982/1678-8060-mioc-118-e230070-gf7.jpg

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