Imaging of immune cell dynamics and host-pathogen interactions in gut-associated lymphoid tissue during Yersinia pseudotuberculosis infections

Principal investigators: Petra Dersch, Jan Rossaint
Project number: CRC 1450 C07
Project term: 01/2021–12/2028

Graphical abstract
© CRC inSight C07

Intestinal infections with Yersinia pseudotuberculosis cause invasion into the gut-associated lymphoid tissues and immune cell recruitment, mainly neutrophils, leading to spatiotemporal re-shaping of the immune response. We found that not only the local environment in infected tissues but also the injection of Yersinia effector proteins (Yops) by the bacteria changed neutrophil abundance and phenotypes. To dissect the mechanism and consequences of this process, we will combine in vivo and in vitro experiments using genetically modified bacteria and mice in disease models using tissue-scale and whole-body imaging.

In order to obtain a high spatio-temporal resolution of the infection process of the gut pathogen Yersinia pseudotuberculosis, we will image the recruitment and dynamics of immune cell populations (1, 2) and characterize Yersinia-targeted immune cells in infected lymphoid tissue of mice (3) during the entire course of the infection. For this purpose, the immune response will be visualized on a cellular level (confocal intravital microscopy) as well as on whole organ levels (e.g. by PET-CT). In this context, we will also analyse the role of platelets (4) for neutrophil recruitment during Yersinia infections and address different neutrophil functions, including NET formation.

In an approach to investigate how Yersinia may escape removal by the immune system and achieve persistence in the gut-associated lymphoid tissues, we will investigate bacterial evasion mechanisms and how they are regulated and manipulated in vivo (5).

Immune cells (neutrophils) infected by enteric bacteria (Yersinia pseudotuberculosis) in a cell culture. Confocal microscopy shows the neutrophil’s cell nuclei (blue), actin (the “skeleton” of the cells, orange) and the bacteria (green). These bacteria lack a specific gene, allowing the immune cells to take them up more efficiently. We are investigating, for example, whether such bacterial mutations give neutrophils an advantage in eradicating the bacteria from the body or whether they help the bacteria survive these immune cells’ attacks.
© Héctor Álvarez Manzo / Petra Dersch's research group

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The names of the principal investigators in our network have been bolded. Publications released prior to 2021, when funding for our network commenced, represent previous project-related work.