Invasion and intracellular replication of Salmonella Typhimurium in epithelial cells

肠炎沙门氏菌血清型鼠伤寒沙门氏菌（S. Typhimurium）是人类和牛肠结肠炎的常见原因，但在易感小鼠中引起系统性伤寒样疾病。这种同时性细胞内病原体侵入非吞噬细胞，如在肠上皮中发现的细胞，并在被称为含沙门氏菌液泡（SCV）的改良吞噬体中存活。两种III型分泌系统（T3SS）将不同的细菌效应蛋白转运到宿主细胞中，是建立细胞内复制环境所必需的。侵袭依赖于T3SS1，而T3SS2是在细胞内诱导的，与细胞内存活/复制和SCV的生物发生有关。最近，我们一直在研究上皮细胞中空泡复制和细胞质复制的相对重要性。在大约5-20%的感染细胞中，鼠伤寒沙门氏菌从液泡中逃逸，并在细胞质中存活和复制。我们发现这些胞质细菌触发非典型的半胱天冬酶4/11炎性小体反应，这对肠上皮的抗菌防御很重要。目前我们正在完成的一项研究表明，在较晚的时间点，T3SS1在细胞质细菌中具有功能活性，而T3SS2仅在液泡细菌中具有功能活性。

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a common cause of enterocolitis in humans and cattle but causes a systemic, typhoid-like, disease in susceptible mice. This facultative intracellular pathogen invades non-phagocytic cells, such as those found in the intestinal epithelium, and survives within a modified phagosome known as the Salmonella-containing vacuoles (SCV). Two type III secretion systems (T3SS), which translocate distinct cohorts of bacterial effector proteins into the host cell, are required for establishment of the intracellular replicative environment. Invasion is dependent on T3SS1 whereas T3SS2 is induced intracellularly and is associated with intracellular survival/replication and biogenesis of the SCV. Recently we have been investigating the relative importance of vacuolar versus cytosolic replication in epithelial cells. In approximately 5-20% of infected cells S. Typhimurium escape from the vacuole and survive and replicate in the cytosol. We have found that these cytosolic bacteria trigger a non canonical caspase 4/11 inflammasome response that is important for antimicrobial defense in the intestinal epithelium. Currently we are completing a study showing that at later time points the T3SS1 is functionally active in the cytosolic bacteria whereas the T3SS2 is functionally active only in the vacuolar bacteria.