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Inflammatory monocytes promote granuloma control of Yersinia infection.

ABSTRACT: 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.

SUBMITTER: Sorobetea D

PROVIDER: S-EPMC10653359 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Inflammatory monocytes promote granuloma control of Yersinia infection.

Sorobetea Daniel D Matsuda Rina R Peterson Stefan T ST Grayczyk James P JP Rao Indira I Krespan Elise E Lanza Matthew M Assenmacher Charles-Antoine CA Mack Matthias M Beiting Daniel P DP Radaelli Enrico E Brodsky Igor E IE

Nature microbiology 20230306 4

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 ...[more]

PMID: 36879169

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Inflammatory monocytes promote granuloma control of Yersinia infection.

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Inflammatory monocytes promote granuloma control of Yersinia infection.

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