Hobbs Laura, Allen Leah, Bias Megan, Johnson Stephanie, DeRespiris Hannah, Diallo Chantal, Bui Loan, Sun Yvonne
Department of Biology, University of Dayton, Dayton, OH, United States.
Front Microbiol. 2021 Sep 1;12:721801. doi: 10.3389/fmicb.2021.721801. eCollection 2021.
is a Gram-positive, intracellular pathogen responsible for the highly fatal foodborne illness listeriosis. Establishing intracellular infections requires the coordinated expressions of a variety of virulence factors, such as the pore-forming toxin listeriolysin O (LLO), in response to various intra- and extracellular signals. For example, we previously reported that differentially modulated LLO production in response to exogenous propionate, a short chain fatty acid either used in salt form as a human food ingredient or produced endogenously by gut microbial fermentation. Therefore, propionate is likely a continuously present signal throughout the transmission and infection process. However, little is known about the role of propionate in modulating host interactions. Here we investigated the impact of propionate treatment on intracellular infections using cell culture infection models. Propionate treatment was performed separately on or host cells before or during infections to better distinguish pathogen-versus-host responses to propionate. Intracellular CFU in RAW264.7 macrophages and plaque diameters in L-fibroblasts were measured as proxy for intracellular infection outcomes. Nitrite levels and cellular morphology were also measured to assess host responses to propionate. We found that propionate pretreatment of anaerobic, but not aerobic, significantly enhanced subsequent intracellular infections in both cell types and nitrite production by infected macrophages. Propionate treatment of uninfected macrophages significantly altered cell morphology, seen by longer cells and greater migration, and reduced nitrite concentration in activated macrophages. Treatment of macrophages with propionate prior to or during infections significantly inhibited intracellular growth of , including those pre-treated with propionate. These results showcased an opposing effect of propionate on intracellular infections and strongly support propionate as an important signaling molecule for both the pathogen and the host cell that can potentially alter the outcome of -host interactions.
是一种革兰氏阳性细胞内病原体，可导致高度致命的食源性疾病李斯特菌病。建立细胞内感染需要响应各种细胞内和细胞外信号，协调表达多种毒力因子，例如形成孔道的毒素李斯特菌溶血素O（LLO）。例如，我们之前报道过，会根据外源性丙酸酯（一种以盐形式用作人类食品成分或由肠道微生物发酵内源性产生的短链脂肪酸）的差异来调节LLO的产生。因此，丙酸酯可能是整个传播和感染过程中持续存在的信号。然而，关于丙酸酯在调节宿主相互作用中的作用知之甚少。在这里，我们使用细胞培养感染模型研究了丙酸酯处理对细胞内感染的影响。在感染前或感染期间分别对或宿主细胞进行丙酸酯处理，以更好地区分病原体与宿主对丙酸酯的反应。测量RAW264.7巨噬细胞中的细胞内菌落形成单位（CFU）和L-成纤维细胞中的噬斑直径，作为细胞内感染结果的指标。还测量了亚硝酸盐水平和细胞形态，以评估宿主对丙酸酯的反应。我们发现，厌氧而非需氧的经丙酸酯预处理后，两种细胞类型中的后续细胞内感染以及受感染巨噬细胞的亚硝酸盐产生均显著增强。对未感染的巨噬细胞进行丙酸酯处理会显著改变细胞形态，表现为细胞更长且迁移能力更强，并降低活化巨噬细胞中的亚硝酸盐浓度。在感染前或感染期间用丙酸酯处理巨噬细胞会显著抑制的细胞内生长，包括那些用丙酸酯预处理过的。这些结果显示了丙酸酯对细胞内感染的相反作用，并有力地支持丙酸酯作为病原体和宿主细胞的重要信号分子，可能会改变宿主相互作用的结果。
