Years of human microbiome research have confirmed that microbes rarely live or function alone, favoring diverse communities. Yet most experimental host-pathogen studies employ single species models of infection. Here, the influence of three-species oral microbial consortium on growth, virulence, invasion and persistence in dendritic cells (DCs) was examined experimentally in human monocyte-derived dendritic cells (DCs) and in patients with periodontitis (PD). Cooperative biofilm formation by Streptococcus gordonii, Fusobacterium nucleatum and Porphyromonas gingivalis was documented in vitro using growth models and scanning electron microscopy. Analysis of growth rates by species-specific 16s rRNA probes revealed distinct, early advantages to consortium growth for S. gordonii and F. nucleatum with P. gingivalis, while P. gingivalis upregulated its short mfa1 fimbriae, leading to increased invasion of DCs. F. nucleatum was only taken up by DCs when in consortium with P. gingivalis. Mature consortium regressed DC maturation upon uptake, as determined by flow cytometry. Analysis of dental plaques of PD and healthy subjects by 16s rRNA confirmed oral colonization with consortium members, but DC hematogenous spread was limited to P. gingivalis and F. nucleatum. Expression of P. gingivalis mfa1 fimbriae was increased in dental plaques and hematogenous DCs of PD patients. P. gingivalis in the consortium correlated with an adverse clinical response in the gingiva of PD subjects. In conclusion, we have identified polymicrobial synergy in a three-species oral consortium that may have negative consequences for the host, including microbial dissemination and adverse peripheral inflammatory responses.

中文翻译：

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口腔生物膜内的多种微生物协同作用促进树突状细胞的入侵和联合体成员的存活。

多年的人类微生物组研究证实，微生物很少单独生活或发挥作用，有利于不同的社区。然而，大多数实验性宿主病原体研究采用单一物种感染模型。在这里，在人类单核细胞衍生的树突细胞 (DC) 和牙周炎 (PD) 患者中，通过实验检查了三种口腔微生物联合体对树突细胞 (DC) 的生长、毒力、侵袭和持久性的影响。使用生长模型和扫描电子显微镜在体外记录了戈登链球菌、具核梭杆菌和牙龈卟啉单胞菌的协同生物膜形成。物种特异性 16s rRNA 探针对生长速率的分析揭示了 S. gordonii 和 F. nucleatum 与 P. gingivalis 的联合生长具有明显的早期优势，而 P. gingivalis 具有明显的早期优势。gingivalis 上调其短 mfa1 菌毛，导致 DCs 的侵袭增加。F. nucleatum 仅在与 P. gingivalis 共生时被 DCs 吸收。如流式细胞术所确定的，成熟的联合体在摄取后使 DC 成熟退化。通过 16s rRNA 对 PD 和健康受试者的牙菌斑进行分析，证实了联合体成员的口腔定植，但 DC 血行传播仅限于 P. gingivalis 和 F. nucleatum。P. gingivalis mfa1 菌毛在 PD 患者的牙菌斑和血源性 DCs 中的表达增加。该联盟中的牙龈卟啉单胞菌与 PD 受试者牙龈中的不良临床反应相关。总之，我们已经确定了可能对宿主产生负面影响的三种口腔联合体中的多种微生物协同作用，