Clark M A, Hirst B H, Jepson M A
Department of Physiological Sciences, Medical School, University of Newcastle upon Tyne, United Kingdom.
Infect Immun. 1998 Feb;66(2):724-31. doi: 10.1128/IAI.66.2.724-731.1998.
In the mouse model of Salmonella typhimurium infection, the specialized antigen-sampling intestinal M cells are the primary route of Salmonella invasion during the early stages of infection. Under certain experimental conditions, M-cell invasion is accompanied by M-cell destruction and loss of adjacent regions of the follicle-associated epithelium (FAE), although the conditions responsible for expression of the cytotoxic phenotype in a proportion of previous studies have not been defined. In the present study, we have demonstrated that the cytotoxic effect exerted by wild-type S. typhimurium on mouse Peyer's patch FAE is dependent on the inoculum composition. We have also demonstrated that the extent of FAE destruction correlates with the extent of M-cell invasion. Bacteria inoculated in Luria-Bertani (LB) broth induce extensive FAE loss and exhibit efficient M-cell invasion, whereas bacteria inoculated in phosphate-buffered saline fail to induce significant FAE disruption and invade M cells at significantly lower levels. Similarly, inoculation in LB significantly enhances invasion of Madin-Darby canine kidney cells by wild-type S. typhimurium. Mutants defective for expression of invA, a component of Salmonella pathogenicity island 1 which is vital for efficient invasion of cultured cells, fail to induce FAE destruction and, when inoculated in LB, are attenuated for M-cell invasion. Variation in inv gene expression is, therefore, one possible mechanism by which inoculate composition may regulate the virulence of wild-type S. typhimurium. Our findings suggest that the composition of the gut luminal contents may be critical in determining the outcome of naturally acquired Salmonella infections and that both vaccine formulation and dietary status of vaccine recipients may significantly affect the efficacy and safety of live Salmonella oral vaccine delivery systems.
在鼠伤寒沙门氏菌感染的小鼠模型中，专门用于抗原采样的肠道M细胞是感染早期沙门氏菌入侵的主要途径。在某些实验条件下，M细胞的入侵伴随着M细胞的破坏以及滤泡相关上皮（FAE）相邻区域的丧失，尽管在先前的一些研究中，导致部分细胞毒性表型表达的条件尚未明确。在本研究中，我们证明了野生型鼠伤寒沙门氏菌对小鼠派伊尔结FAE施加的细胞毒性作用取决于接种物的组成。我们还证明了FAE破坏的程度与M细胞入侵的程度相关。接种在Luria-Bertani（LB）肉汤中的细菌会导致广泛的FAE丧失，并表现出高效的M细胞入侵，而接种在磷酸盐缓冲盐水中的细菌则不会引起显著的FAE破坏，并且以显著较低的水平入侵M细胞。同样，接种在LB中可显著增强野生型鼠伤寒沙门氏菌对Madin-Darby犬肾细胞的入侵。invA是沙门氏菌致病岛1的一个组成部分，对培养细胞的有效入侵至关重要，缺乏invA表达的突变体无法诱导FAE破坏，并且当接种在LB中时，其对M细胞的入侵能力减弱。因此，inv基因表达的变化可能是接种物组成调节野生型鼠伤寒沙门氏菌毒力的一种可能机制。我们的研究结果表明，肠道腔内内容物的组成可能对确定自然获得性沙门氏菌感染的结果至关重要，并且疫苗配方和疫苗接种者的饮食状况可能会显著影响活沙门氏菌口服疫苗递送系统的疗效和安全性。
