Foster N, Lovell M A, Marston K L, Hulme S D, Frost A J, Bland P, Barrow P A
Division of Environmental Microbiology, Institute for Animal Health, Compton Laboratory, Compton, Newbury, Berkshire RG20 7NN, United Kingdom.
Infect Immun. 2003 Apr;71(4):2182-91. doi: 10.1128/IAI.71.4.2182-2191.2003.
Oral inoculation of 5-day-old gnotobiotic pigs with Salmonella enterica serovar Typhimurium strain F98 resulted in severe enteritis and invasive disease. Preinoculation 24 h earlier with an avirulent mutant of Salmonella enterica serovar Infantis (1326/28) completely prevented disease for up to 14 days (when the experiment was terminated). S. enterica serovar Infantis colonized the alimentary tract well, with high bacterial counts in the intestinal lumen but with almost no invasion into the tissues. Unprotected pigs had high S. enterica serovar Typhimurium counts in the intestines, blood, and major nonintestinal organs. Recovery of this strain from the blood and major organs in S. enterica serovar Infantis-protected pigs was substantially reduced despite the fact that intestinal counts were also very high. Protection against disease thus did not involve a colonization exclusion phenomenon. Significant (P < 0.05) infiltration of monocytes/macrophages was observed in the submucosal regions of the intestines of both S. enterica serovar Infantis-protected S. enterica serovar Typhimurium-challenged pigs and unprotected S. enterica serovar Typhimurium-challenged pigs. However, only polymorphonuclear neutrophils (PMNs) were observed throughout the villus, where significant (P < 0.05) numbers infiltrated the lamina propria and the subnuclear and supranuclear regions of the epithelia, indicating that PMN induction and positioning following S. enterica serovar Infantis inoculation was consistent with rapid protection against the challenge strain. Similarly, in vitro experiments using a human fetal intestinal epithelial cell line (INT 407) demonstrated that, although significantly (P < 0.05) fewer S. enterica serovar Infantis than S. enterica serovar Typhimurium organisms invaded the monolayers, S. enterica serovar Infantis induced an NF-kappaB response and significantly (P < 0.05) raised interleukin 8 levels and transmigration of porcine PMN. The results of this study suggest that attenuated Salmonella strains can protect the immature intestine against clinical salmonellosis by PMN induction. They also demonstrate that PMN induction is not necessarily associated with clinical symptoms and/or intestinal pathology.
用肠炎沙门氏菌鼠伤寒血清型F98对5日龄无菌猪进行口服接种会导致严重肠炎和侵袭性疾病。提前24小时用无毒的肠炎沙门氏菌婴儿血清型突变株（1326/28）进行接种，可在长达14天内（实验终止时）完全预防疾病。肠炎沙门氏菌婴儿血清型能很好地定殖于消化道，肠腔内细菌数量很高，但几乎没有侵入组织。未受保护的猪在肠道、血液和主要非肠道器官中的肠炎沙门氏菌鼠伤寒血清型数量很高。尽管肠炎沙门氏菌婴儿血清型保护的猪肠道中的菌数也很高，但从其血液和主要器官中分离到该菌株的数量大幅减少。因此，对疾病的保护并不涉及定殖排斥现象。在肠炎沙门氏菌婴儿血清型保护的肠炎沙门氏菌鼠伤寒血清型攻击猪和未受保护的肠炎沙门氏菌鼠伤寒血清型攻击猪的肠道黏膜下层区域均观察到单核细胞/巨噬细胞的显著（P<0.05）浸润。然而，仅在整个绒毛中观察到多形核中性粒细胞（PMN），其中有显著（P<0.05）数量的PMN浸润到固有层以及上皮细胞的核下和核上区域，这表明肠炎沙门氏菌婴儿血清型接种后PMN的诱导和定位与对攻击菌株的快速保护一致。同样，使用人胎儿肠上皮细胞系（INT 407）进行的体外实验表明，尽管侵入单层细胞的肠炎沙门氏菌婴儿血清型比肠炎沙门氏菌鼠伤寒血清型明显（P<0.05）少，但肠炎沙门氏菌婴儿血清型诱导了NF-κB反应，并显著（P<0.05）提高了白细胞介素8水平以及猪PMN 的迁移率。本研究结果表明，减毒沙门氏菌菌株可通过诱导PMN保护未成熟肠道免受临床沙门氏菌病感染。它们还表明，PMN诱导不一定与临床症状和/或肠道病理相关。
