Kamada Nobuhiko, Sakamoto Kei, Seo Sang-Uk, Zeng Melody Y, Kim Yun-Gi, Cascalho Marilia, Vallance Bruce A, Puente José L, Núñez Gabriel
Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Cell Host Microbe. 2015 May 13;17(5):617-27. doi: 10.1016/j.chom.2015.04.001. Epub 2015 Apr 30.
Virulence factors expressed by enteric bacteria are pivotal for pathogen colonization and induction of intestinal disease, but the mechanisms by which host immunity regulates pathogen virulence are largely unknown. Here we show that specific antibody responses are required for downregulation of virulence gene expression in Citrobacter rodentium, an enteric pathogen that models human infections with attaching-and-effacing bacteria. In the absence of antibodies against the pathogen, phenotypically virulent C. rodentium, accumulated and infected the epithelium and subsequently invaded the lamina propia, causing host lethality. IgG induced after infection recognized virulence factors and bound virulent bacteria within the intestinal lumen, leading to their engulfment by neutrophils, while phenotypically avirulent pathogens remained in the intestinal lumen and were eventually outcompeted by the microbiota. Thus, the interplay of the innate and adaptive immune system selectively targets virulent C. rodentium in the intestinal lumen to promote pathogen eradication and host survival.
肠道细菌表达的毒力因子对于病原体的定植和肠道疾病的诱导至关重要,但宿主免疫调节病原体毒力的机制在很大程度上尚不清楚。在这里,我们表明,特异性抗体反应是下调鼠柠檬酸杆菌毒力基因表达所必需的,鼠柠檬酸杆菌是一种肠道病原体,可模拟人类被黏附-抹除性细菌感染的情况。在缺乏针对该病原体的抗体时,表型有毒的鼠柠檬酸杆菌会积累并感染上皮细胞,随后侵入固有层,导致宿主死亡。感染后诱导产生的IgG识别毒力因子并结合肠腔内的有毒细菌,导致它们被中性粒细胞吞噬,而表型无毒的病原体则留在肠腔内,最终被微生物群淘汰。因此,先天性和适应性免疫系统的相互作用选择性地靶向肠腔内有毒的鼠柠檬酸杆菌,以促进病原体的根除和宿主的存活。