An innate granuloma eradicates an environmental pathogen using Gsdmd and Nos2

Carissa K. Harvest, Taylor J. Abele, Chen Yu, Cole J. Beatty, Megan E. Amason, Zachary P. Billman, Morgan A. DePrizio, Fernando W. Souza, Carolyn A. Lacey, Vivien I. Maltez, Heather N. Larson, Benjamin D. McGlaughon, Daniel R. Saban, Stephanie A. Montgomery and Edward A. Miao ()
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Carissa K. Harvest: Duke University School of Medicine
Taylor J. Abele: Duke University School of Medicine
Chen Yu: Duke University School of Medicine
Cole J. Beatty: Duke University School of Medicine
Megan E. Amason: Duke University School of Medicine
Zachary P. Billman: Duke University School of Medicine
Morgan A. DePrizio: Duke University School of Medicine
Fernando W. Souza: Duke University School of Medicine
Carolyn A. Lacey: Duke University School of Medicine
Vivien I. Maltez: University of North Carolina at Chapel Hill
Heather N. Larson: Duke University School of Medicine
Benjamin D. McGlaughon: University of North Carolina at Chapel Hill
Daniel R. Saban: Duke University School of Medicine
Stephanie A. Montgomery: University of North Carolina at Chapel Hill
Edward A. Miao: Duke University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract Granulomas often form around pathogens that cause chronic infections. Here, we discover an innate granuloma model in mice with an environmental bacterium called Chromobacterium violaceum. Granuloma formation not only successfully walls off, but also clears, the infection. The infected lesion can arise from a single bacterium that replicates despite the presence of a neutrophil swarm. Bacterial replication ceases when macrophages organize around the infection and form a granuloma. This granuloma response is accomplished independently of adaptive immunity that is typically required to organize granulomas. The C. violaceum-induced granuloma requires at least two separate defense pathways, gasdermin D and iNOS, to maintain the integrity of the granuloma architecture. This innate granuloma successfully eradicates C. violaceum infection. Therefore, this C. violaceum-induced granuloma model demonstrates that innate immune cells successfully organize a granuloma and thereby resolve infection by an environmental pathogen.

Date: 2023
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DOI: 10.1038/s41467-023-42218-1

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