An innate granuloma eradicates an environmental pathogen usingGsdmdandNos2

Abstract

SUMMARYGranulomas often form around pathogens that cause chronic infections. Here, we discover a novel granuloma model in mice.Chromobacterium violaceumis an environmental bacterium that stimulates granuloma formation that not only successfully walls off but also clears the infection. The infected lesion can arise from a single bacterium that replicates in 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. TheC. violaceum-induced granuloma requires at least two separate defense pathways, gasdermin D and iNOS, to maintain the integrity of the granuloma architecture. These innate granulomas successfully eradicateC. violaceuminfection. Therefore, this newC. violaceum-induced granuloma model demonstrates that innate immune cells successfully organize a granuloma and thereby eradicate infection by an environmental pathogen.