Sorobetea, Daniel and Matsuda, Rina and Peterson, Stefan T. and Grayczyk, James P. and Rao, Indira and Krespan, Elise and Lanza, Matthew and Assenmacher, Charles-Antoine and Mack, Matthias and Beiting, Daniel P. and Radaelli, Enrico and Brodsky, Igor E. (2023) Inflammatory monocytes promote granuloma control of Yersinia infection. NATURE MICROBIOLOGY, 8 (4). 666-+. ISSN 2058-5276,
Full text not available from this repository. (Request a copy)Abstract
Enteric Yersinia pseudotuberculosis infection is contained by host inflammatory monocyte-driven pyogranuloma formation to counter bacterial YopH-dependent anti-neutrophil activity. Granulomas are organized immune cell aggregates formed in response to chronic infection or antigen persistence. The bacterial pathogen Yersinia pseudotuberculosis (Yp) blocks innate inflammatory signalling and immune defence, inducing neutrophil-rich pyogranulomas (PGs) within lymphoid tissues. Here we uncover that Yp also triggers PG formation within the murine intestinal mucosa. Mice lacking circulating monocytes fail to form defined PGs, have defects in neutrophil activation and succumb to Yp infection. Yersinia lacking virulence factors that target actin polymerization to block phagocytosis and reactive oxygen burst do not induce PGs, indicating that intestinal PGs form in response to Yp disruption of cytoskeletal dynamics. Notably, mutation of the virulence factor YopH restores PG formation and control of Yp in mice lacking circulating monocytes, demonstrating that monocytes override YopH-dependent blockade of innate immune defence. This work reveals an unappreciated site of Yersinia intestinal invasion and defines host and pathogen drivers of intestinal granuloma formation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LYMPH-NODES; PSEUDOTUBERCULOSIS; BACTERIAL; EXPRESSION; CELLS; NEUTROPHIL; ACTIVATION; ENTEROCOLITICA; RESPONSES; YOPH; |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Mar 2024 12:48 |
| Last Modified: | 13 Mar 2024 12:48 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59927 |
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