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: 01/2021–12/2024

Graphical abstract
© CRC inSight

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

Team

Principal investigators

Project members

Publications

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.

2023

Ludwig N, Thörner-van Almsick J, Mersmann S, Bardel B, Niemann S, Chasan AI, Schäfers M, Margraf A, Rossaint J, Kahl BC, Zarbock A, Block H. Nuclease activity and protein A release of Staphylococcus aureus clinical isolates determine the virulence in a murine model of acute lung infection. Front. Immunol. 2023;14Abstract

2022

Block H, Rossaint J, Zarbock A. The Fatal Circle of NETs and NET-Associated DAMPs Contributing to Organ Dysfunction. Cells 2022;11Abstract
Revenstorff J, Ludwig N, Hilger A, Mersmann S, Lehmann M, Grenzheuser JC, Kardell M, Bone J, Kotting NM, Marx NC, Roth J, Vogl T, Rossaint J. Role of S100A8/A9 in Platelet-Neutrophil Complex Formation during Acute Inflammation. Cells 2022;11Abstract

2021

Machtakova M, Wirsching S, Gehring S, Landfester K, Therien-Aubin H. Controlling the semi-permeability of protein nanocapsules influences the cellular response to macromolecular payloads. J Mater Chem B 2021;9: 8389-8398. Abstract
Rossaint J, Thomas K, Mersmann S, Skupski J, Margraf A, Tekath T, Jouvene CC, Dalli J, Hidalgo A, Meuth SG, Soehnlein O, Zarbock A. Platelets orchestrate the resolution of pulmonary inflammation in mice by T reg cell repositioning and macrophage education. J Exp Med 2021;218: e20201353. Abstract

2018

Gran S, Honold L, Fehler O, Zenker S, Eligehausen S, Kuhlmann MT, Geven E, den Bosch M van, van Lent P, Spiekermann C, Hermann S, Vogl T, Schäfers M, Roth J. Imaging, myeloid precursor immortalization, and genome editing for defining mechanisms of leukocyte recruitment_in vivo_. Theranostics 2018;8: 2407-2423. Abstract
Heine W, Beckstette M, Heroven AK, Thiemann S, Heise U, Nuss AM, Pisano F, Strowig T, Dersch P. Loss of CNFY toxin-induced inflammation drives Yersinia pseudotuberculosis into persistency. PLoS Pathog 2018;14: e1006858. Abstract
Rossaint J, Margraf A, Zarbock A. Role of Platelets in Leukocyte Recruitment and Resolution of Inflammation. Front Immunol 2018;9: 2712. Abstract

2017

Nuss AM, Beckstette M, Pimenova M, Schmuhl C, Opitz W, Pisano F, Heroven AK, Dersch P. Tissue dual RNA-seq allows fast discovery of infection-specific functions and riboregulators shaping host-pathogen transcriptomes. Proc Natl Acad Sci U S A 2017;114: E791-E800. Abstract
Pezoldt J, Pisano F, Heine W, Pasztoi M, Rosenheinrich M, Nuss AM, Pils MC, Prinz I, Forster R, Huehn J, Dersch P. Impact of CCR7 on T-Cell Response and Susceptibility to Yersinia pseudotuberculosis Infection. J Infect Dis 2017;216: 752-760. Abstract

2016

Rossaint J, Kuhne K, Skupski J, Van Aken H, Looney MR, Hidalgo A, Zarbock A. Directed transport of neutrophil-derived extracellular vesicles enables platelet-mediated innate immune response. Nat Commun 2016;7: 13464. Abstract
Rossaint J, Oehmichen J, Van Aken H, Reuter S, Pavenstadt HJ, Meersch M, Unruh M, Zarbock A. FGF23 signaling impairs neutrophil recruitment and host defense during CKD. J Clin Invest 2016;126: 962-974. Abstract

2015

Avican K, Fahlgren A, Huss M, Heroven AK, Beckstette M, Dersch P, Fallman M. Reprogramming of Yersinia from virulent to persistent mode revealed by complex in vivo RNA-seq analysis. PLoS Pathog 2015;11: e1004600. Abstract
Rossaint J, Berger C, Kraft F, Van Aken H, Giesbrecht N, Zarbock A. Hydroxyethyl starch 130/04 decreases inflammation, neutrophil recruitment, and neutrophil extracellular trap formation. Br J Anaesth 2015;114: 509-519. Abstract

2014

Sreeramkumar V, Adrover JM, Ballesteros I, Cuartero MI, Rossaint J, Bilbao I, Nacher M, Pitaval C, Radovanovic I, Fukui Y, McEver RP, Filippi M-D, Lizasoain I, Ruiz-Cabello J, Zarbock A, Moro MA, Hidalgo A. Neutrophils scan for activated platelets to initiate inflammation. Science 2014;346: 1234-1238. Abstract

2013

Schweer J, Kulkarni D, Kochut A, Pezoldt J, Pisano F, Pils MC, Genth H, Huehn J, Dersch P. The cytotoxic necrotizing factor of Yersinia pseudotuberculosis (CNFY) enhances inflammation and Yop delivery during infection by activation of Rho GTPases. PLoS Pathog 2013;9: e1003746. Abstract

2006

Heise T, Dersch P. Identification of a domain in Yersinia virulence factor YadA that is crucial for extracellular matrix-specific cell adhesion and uptake. Proc Natl Acad Sci U S A 2006;103: 3375-3380. Abstract