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Neutrophils are dispensable for Shigella control: macrophages take centre stage

Nature Reviews Immunology volume 25, page 233 (2025)Cite this article

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Shigellosis is a highly contagious and severe gastrointestinal infection caused by bacteria of the genus Shigella. Whereas exposure to a small number of Shigella bacteria can cause disease in humans, mice are naturally resistant. However, mice deficient in the NAIP–NLRC4 inflammasome and caspase-11 (Nlrc4−/−Casp11−/− mice) have recently emerged as a genetically tractable model to study human shigellosis. Shigella infection has been shown to recruit myeloid cells, but the specific roles of macrophages and neutrophils remain understudied.

In a recent preprint (not peer-reviewed), Eislmayr et al. investigate the roles of neutrophils and macrophages in controlling Shigella infection and in disease pathogenesis in Nlrc4−/−Casp11−/− mice. They show that IFNγ neutralization leads to severe shigellosis, characterized by increased bacteria in intestinal epithelial cells (IECs), increased bacterial translocation to mesenteric lymph nodes and spleen, and increased pro-inflammatory cytokines in the lamina propria. Similarly, Ifngr−/−Nlrc4−/−Casp11−/− mice have more severe disease than Nlrc4−/−Casp11−/− mice, underscoring a role for IFNγ in host protection.

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References

Original article

  • Eislmayr, K. D. et al. Macrophages orchestrate elimination of Shigella from the intestinal epithelial cell niche via TLR-induced IL-12 and IFN-γ. Preprint at bioRxiv https://doi.org/10.1101/2025.01.20.633976 (2025)

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  1. Preprint Club, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Didem Ağaç Çobanoğlu & James P. Allison

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  1. Didem Ağaç Çobanoğlu
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  2. James P. Allison
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Correspondence to Didem Ağaç Çobanoğlu.

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Ağaç Çobanoğlu, D., Allison, J.P. Neutrophils are dispensable for Shigella control: macrophages take centre stage. Nat Rev Immunol 25, 233 (2025). https://doi.org/10.1038/s41577-025-01157-2

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  • DOI: https://doi.org/10.1038/s41577-025-01157-2

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