Kløve Sigri, Genger Claudia, Mousavi Soraya, Weschka Dennis, Bereswill Stefan, Heimesaat Markus M
Institute of Microbiology, Infectious Diseases and Immunology, Charité - University Medicine Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, Germany.
Pathogens. 2020 May 18;9(5):386. doi: 10.3390/pathogens9050386.
Zoonotic , including and , are among the most prevalent agents of food-borne enteritis worldwide. The immunopathological sequelae of campylobacteriosis are caused by Toll-like Receptor-4 (TLR4)-dependent host immune responses, induced by bacterial lipooligosaccharide (LOS). In order to investigate -host interactions, including the roles of the human gut microbiota and TLR4, upon infection, we applied a clinical acute campylobacteriosis model, and subjected secondary abiotic, TLR4-deficient IL10 mice and IL10 controls to fecal microbiota transplantation derived from human donors by gavage, before peroral challenge. Until day 21 post-infection, could stably colonize the gastrointestinal tract of human microbiota-associated (hma) mice of either genotype. TLR4-deficient IL10 mice, however, displayed less severe clinical signs of infection, that were accompanied by less distinct apoptotic epithelial cell and innate as well as adaptive immune cell responses in the colon, as compared to IL10 counterparts. Furthermore, infected IL10, as opposed to TLR4-deficient IL10, mice displayed increased pro-inflammatory cytokine concentrations in intestinal and, strikingly, systemic compartments. We conclude that pathogenic LOS might play an important role in inducing TLR4-dependent host immune responses upon infection, which needs to be further addressed in more detail.
人畜共患病原体，包括[具体病原体1]和[具体病原体2]，是全球食源性肠炎最常见的病原体之一。弯曲菌病的免疫病理后遗症是由细菌脂寡糖（LOS）诱导的Toll样受体4（TLR4）依赖性宿主免疫反应引起的。为了研究感染时[病原体名称]与宿主的相互作用，包括人类肠道微生物群和TLR4的作用，我们应用了临床急性弯曲菌病模型，并在口服[病原体名称]攻击前，通过灌胃将来自人类供体的粪便微生物群移植到二代无菌、TLR4缺陷的IL10小鼠和IL10对照小鼠体内。直到感染后第21天，[病原体名称]能够稳定定殖于两种基因型的人类微生物群相关（hma）小鼠的胃肠道。然而，与IL10对照小鼠相比，TLR4缺陷的IL10小鼠表现出较轻的感染临床症状，结肠中凋亡上皮细胞以及固有免疫和适应性免疫细胞反应也不那么明显。此外，与TLR4缺陷的IL10小鼠相比，感染[病原体名称]的IL10小鼠在肠道以及显著的全身各腔室中促炎细胞因子浓度升高。我们得出结论，致病性LOS可能在[病原体名称]感染时诱导TLR4依赖性宿主免疫反应中起重要作用，这需要进一步更详细地研究。
