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
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).
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.
|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|
|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|
|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|
|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|
|Rossaint J, Herter JM, Van Aken H, Napirei M, Doring Y, Weber C, Soehnlein O, Zarbock A. Synchronized integrin engagement and chemokine activation is crucial in neutrophil extracellular trap-mediated sterile inflammation. Blood 2014;123: 2573-2584. Abstract|
|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|
|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|