Oral Infection with Signature-Tagged Listeria monocytogenes Reveals Organ-Specific Growth and Dissemination Routes in Guinea Pigs

Abstract

ABSTRACTListeria monocytogenescauses a serious food-borne disease due to its ability to spread from the intestine to other organs, a process that is poorly understood. In this study we used 20 signature-tagged wild-type clones ofL. monocytogenesin guinea pigs in combination with extensive quantitative data analysis to gain insight into extraintestinal dissemination. We show thatL. monocytogenescolonized the liver in all asymptomatic animals. Spread to the liver occurred as early as 4 h after ingestion via a direct pathway from the intestine to the liver. This direct pathway contributed significantly to the bacterial load in the liver and was followed by a second wave of dissemination via the mesenteric lymph nodes (indirect pathway). Furthermore, bacteria were eliminated in the liver, whereas small intestinal villi provided a niche for bacterial replication, indicating organ-specific differences in net bacterial growth. Bacteria were shed back from intestinal villi into the small intestinal lumen and reinfected the Peyer's patches. Together, these results support a novel dissemination model whereL. monocytogenesreplicates in intestinal villi, is shed into the lumen, and reinfects intestinal immune cells that traffic to liver and mesenteric lymph nodes, a process that occurs even during asymptomatic colonization.