Department of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, China.
Laboratory of Immunology, Brain Korea 21 PLUS Project for Medical Science, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
Infect Immun. 2018 Dec 19;87(1). doi: 10.1128/IAI.00654-18. Print 2019 Jan.
is a Gram-negative enteropathogen and causes gastrointestinal infections. It disseminates from gut to mesenteric lymph nodes (MLNs), spleen, and liver of infected humans and animals. Although the molecular mechanisms for dissemination and infection are unclear, many Gram-negative enteropathogens presumably invade the small intestine via Peyer's patches to initiate dissemination. In this study, we demonstrate that utilizes its lipopolysaccharide (LPS) core to interact with CD209 receptors, leading to invasion of human dendritic cells (DCs) and murine macrophages. These -CD209 interactions result in bacterial dissemination to MLNs, spleens, and livers of both wild-type and Peyer's patch-deficient mice. The blocking of the -CD209 interactions by expression of O-antigen and with oligosaccharides reduces infectivity. Based on the well-documented studies in which HIV-CD209 interaction leads to viral dissemination, we therefore propose an infection route for where this pathogen, after penetrating the intestinal mucosal membrane, hijacks the -CD209 interaction antigen-presenting cells to reach their target destinations, MLNs, spleens, and livers.
是一种革兰氏阴性肠道病原体,可引起胃肠道感染。它从肠道传播到受感染人类和动物的肠系膜淋巴结(MLN)、脾脏和肝脏。尽管传播和感染的分子机制尚不清楚,但许多革兰氏阴性肠道病原体可能通过派尔集合淋巴结侵入小肠以开始传播。在这项研究中,我们证明了利用其脂多糖(LPS)核心与 CD209 受体相互作用,导致人类树突状细胞(DC)和鼠巨噬细胞的入侵。这些 -CD209 相互作用导致细菌传播到 MLN、脾脏和野生型和派尔集合淋巴结缺陷小鼠的肝脏。通过表达 O-抗原和寡糖来阻断 -CD209 相互作用可降低感染性。基于 HIV-CD209 相互作用导致病毒传播的已有充分记录的研究,因此我们提出了一种感染途径,即该病原体穿透肠黏膜后,劫持 -CD209 相互作用的抗原呈递细胞到达其目标目的地,即 MLN、脾脏和肝脏。