Abstract
Yersinia enterocolitica (Ye) evades the immune system of the host by injection of Yersinia outer proteins (Yops) via a type three secretion system into host cells. In this study, a reporter system comprising a YopE-β-lactamase hybrid protein and a fluorescent staining sensitive to β-lactamase cleavage was used to track Yop injection in cell culture and in an experimental Ye mouse infection model. Experiments with GD25, GD25-β1A, and HeLa cells demonstrated that β1-integrins and RhoGTPases play a role for Yop injection. As demonstrated by infection of splenocyte suspensions in vitro, injection of Yops appears to occur randomly into all types of leukocytes. In contrast, upon infection of mice, Yop injection was detected in 13% of F4/80+, 11% of CD11c+, 7% of CD49b+, 5% of Gr1+ cells, 2.3% of CD19+, and 2.6% of CD3+ cells. Taking the different abundance of these cell types in the spleen into account, the highest total number of Yop-injected cells represents B cells, particularly CD19+CD21+CD23+ follicular B cells, followed by neutrophils, dendritic cells, and macrophages, suggesting a distinct cellular tropism of Ye. Yop-injected B cells displayed a significantly increased expression of CD69 compared to non-Yop-injected B cells, indicating activation of these cells by Ye. Infection of IFN-γR (receptor)- and TNFRp55-deficient mice resulted in increased numbers of Yop-injected spleen cells for yet unknown reasons. The YopE-β-lactamase hybrid protein reporter system provides new insights into the modulation of host cell and immune responses by Ye Yops.
Highlights
Yersinia enterocolitica (Ye) is an enteropathogenic bacterium that causes gastrointestinal disorders such as enteritis and enterocolitis as well as extraintestinal manifestations such as lymphadenitis, reactive arthritis, and septicemia [1,2]
Tracking of cells in which Yersinia outer proteins (Yops) injection occurred has only been described for Yersinia pestis far
We demonstrated that b1-integrins and the RhoGTPases RhoA and Rac1 are involved in Yop injection
Summary
Yersinia enterocolitica (Ye) is an enteropathogenic bacterium that causes gastrointestinal disorders such as enteritis and enterocolitis as well as extraintestinal manifestations such as lymphadenitis, reactive arthritis, and septicemia [1,2]. Ye needs to evade the host’s immune defense. Ye evolved a type III secretion system (TTSS) consisting of an injectisome and effector proteins the latter of which are injected into host cells [3]. The injection of effectors into host cells via a TTSS injectisome is a common strategy of pathogenic bacteria to counteract the host’s immune response [4]. The TTSS injectisome is complex ATP-driven protein-export machinery. Built of ring shaped proteins, the basal body is providing a channel through the bacterial membranes and the periplasm or the peptidoglycan wall, respectively. Pore-forming proteins enable the injection of the effector proteins through the membrane of host target cells [7,8]
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