Transcytosis pathways used by Salmonella enterica and Mycobacterium avium for translocation across the intestinal epithelial barrier

肠上皮负责营养吸收和液体平衡，但也表现出作为物理和先天免疫屏障的基本功能，致力于保护身体免受肠道和病原微生物的侵袭。许多病原体已经进化出使它们能够突破上皮屏障破坏宿主细胞功能以存活、复制和传播的机制。沙门氏菌和分枝杆菌是重要的人类和动物病原体。此外，一些致病性分枝杆菌物种，如M。鸟类亚种是肠侵入性的，并使用肠道作为进入口。常见于Samonella和M.鸟类亚种的一个重要特征是它们靶向不同类型的肠上皮细胞以进入宿主的能力。对于这两种病原体来说，这可能是最重要的，因为用于易位的细胞类型可能在很大程度上决定感染过程的下一步。在本研究中，我们重点研究了沙门氏菌和M.特别是在胞吞区室和胞吐途径方面，我们的目的是确定如何沙门氏菌肠道血清型和不同的M。鸟类亚种通过和离开极化的肠上皮细胞，并表征宿主细胞途径和涉及的细菌因子。

The intestinal epithelium is responsible for nutrient uptake and fluid balance, but also exhibits essential functions as a physical and innate immune barrier devoted to protecting the body against invasion of both commensal and pathogenic microorganisms. Many pathogens have evolved mechanisms that enable them to breach the epithelial barrier subverting host cell functions in order to survive, replicate, and disseminate. Salmonella and mycobacteria are important human and animal pathogens. Also, some pathogenic mycobacterial species such as the M. avium subspecies are enteroinvasive and use the intestinal tract as port of entry. Common to Samonella and M. avium subspecies is their capacity to target different types of intestinal epithelial cells for host entry. For both pathogens this might be of utmost importance since the type of cell used for translocation might considerably determine the next steps of the infection process. In this proposal we are focusing on the mechanisms of transcytosis of Salmonella and M. avium across the intestinal epithelium with special regard to the transcytotic compartments and exocytosis pathways. We aim to determine how Salmonella enterica serovars and different M. avium subspecies pass through and exit from polarized intestinal epithelial cells and characterize host cell pathways and the bacterial factors involved.