A TNF-IL-1 circuit controls Yersinia within intestinal pyogranulomas

Rina Matsuda, Daniel Sorobetea, Jenna Zhang, Stefan T. Peterson, James P. Grayczyk, Winslow Yost, Nicolai Apenes, Maria E. Kovalik, Beatrice Herrmann, Rosemary J. O’neill, Andrea C. Bohrer, Matthew Lanza, Charles Antoine Assenmacher, Katrin D. Mayer-Barber, Sunny Shin, Igor E. Brodsky

Research output: Contribution to journalArticlepeer-review

Abstract

Tumor necrosis factor (TNF) is a pleiotropic inflammatory cytokine that mediates antimicrobial defense and granuloma formation in response to infection by numerous pathogens. We previously reported that Yersinia pseudotuberculosis colonizes the intestinal mucosa and induces the recruitment of neutrophils and inflammatory monocytes into organized immune structures termed pyogranulomas (PG) that control Yersinia infection. Inflammatory monocytes are essential for the control and clearance of Yersinia within intestinal PG, but how monocytes mediate Yersinia restriction is poorly understood. Here, we demonstrate that TNF signaling in monocytes is required for bacterial containment following enteric Yersinia infection. We further show that monocyte-intrinsic TNFR1 signaling drives the production of monocyte-derived interleukin-1 (IL-1), which signals through IL-1 receptors on non-hematopoietic cells to enable PG-mediated control of intestinal Yersinia infection. Altogether, our work reveals a monocyte-intrinsic TNF-IL-1 collaborative inflammatory circuit that restricts intestinal Yersinia infection.

Original languageEnglish (US)
Article numbere20230679
JournalJournal of Experimental Medicine
Volume221
Issue number3
DOIs
StatePublished - 2024

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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