Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France; IHU-Méditerranée Infection, Marseille, France.
Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France; IHU-Méditerranée Infection, Marseille, France.
Microb Pathog. 2021 Sep;158:105074. doi: 10.1016/j.micpath.2021.105074. Epub 2021 Jun 25.
Tropheryma whipplei is a bacterial pathogen responsible for a wide range of infections in humans, covering asymptomatic carriage, acute infections, chronic isolated infections and classic Whipple's disease. Although the bacterium is commonly found in the environment, it very rarely causes disease. Genetic comparison of clinical isolates has revealed that main variations were found in region encoding T. whipplei surface glycoproteins called WiSP. However, no association has been made between the genetic diversity and the clinical manifestations of the infection. In this study we evaluated the phenotypic diversity of 26 clinical isolates from different origins and taken from patient with different infection outcomes. MRC5 and macrophages cells were infected, and bacterial uptake, survival and the pro-and anti-inflammatory potential of the different clinical isolates was assessed. No significant difference of phagocytosis was found between the different isolates; however, we found that bacterial replication was increased for bacteria expressing high molecular weight WiSP. In addition, we found that the expression of the genes coding for IL-1β and TGF-β was significantly higher when MRC5 cells were stimulated with isolates from chronic infections compared to isolates from localized infections while no significant differences were observed in macrophages. Overall, our study revealed that, as previously observed at the genetic level, phenotypic diversity of T. whipplei isolates is associated with the expression of different WiSP, which may result in subtle differences in host responses. Other host factors or genetic predisposition may explain the range of clinical manifestations of T. whipplei infections.
特罗斐姆热希佩尔氏菌是一种细菌病原体，可引起人类多种感染，包括无症状携带、急性感染、慢性孤立性感染和典型的惠普尔病。尽管该细菌在环境中很常见，但很少引起疾病。对临床分离株的基因比较表明，主要变异存在于编码特罗斐姆热希佩尔氏菌表面糖蛋白的 WiSP 区域。然而，尚未发现遗传多样性与感染临床表现之间存在关联。在这项研究中，我们评估了来自不同来源的 26 个临床分离株的表型多样性，这些分离株取自具有不同感染结果的患者。我们感染了 MRC5 和巨噬细胞，并评估了不同临床分离株的细菌摄取、存活以及促炎和抗炎潜力。我们发现不同分离株之间的吞噬作用没有显著差异；然而，我们发现表达高分子量 WiSP 的细菌的细菌复制增加了。此外，我们发现当 MRC5 细胞受到慢性感染分离株刺激时，编码 IL-1β 和 TGF-β 的基因表达显著高于受到局部感染分离株刺激时，而在巨噬细胞中未观察到显著差异。总体而言，我们的研究表明，与先前在遗传水平上观察到的一样，特罗斐姆热希佩尔氏菌分离株的表型多样性与不同 WiSP 的表达相关，这可能导致宿主反应的细微差异。其他宿主因素或遗传易感性可能解释了特罗斐姆热希佩尔氏菌感染的临床表现范围。
