An innate granuloma eradicates an environmental pathogen using Gsdmd and Nos2

Author:

Harvest Carissa K.,Abele Taylor J.ORCID,Yu ChenORCID,Beatty Cole J.ORCID,Amason Megan E.ORCID,Billman Zachary P.,DePrizio Morgan A.,Souza Fernando W.,Lacey Carolyn A.ORCID,Maltez Vivien I.,Larson Heather N.ORCID,McGlaughon Benjamin D.,Saban Daniel R.,Montgomery Stephanie A.,Miao Edward A.ORCID

Abstract

AbstractGranulomas 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.

Funder

U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases

National Science Foundation

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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