Author:
Leiba Jade,Sipka Tamara,Begon-Pescia Christina,Bernardello Matteo,Tairi Sofiane,Bossi Lionello,Gonzalez Anne-Alicia,Mialhe Xavier,Gualda Emilio J.,Loza-Alvarez Pablo,Blanc-Potard Anne,Lutfalla Georges,Nguyen-Chi Mai
Abstract
ABSTRACTNumerous intracellular bacterial pathogens interfere with macrophage function, including macrophage polarization, to establish a niche and persist. However, the spatiotemporal dynamics of macrophage polarization during infection within host remain to be investigated. Here, we implement a model of persistentSalmonellaTyphimurium infection in zebrafish, which allows visualization of polarized macrophages and bacteria in real time at high-resolution. While macrophages polarize toward M1-like phenotype to control early infection, during later stages,Salmonellapersists inside non-inflammatory clustered macrophages. Transcriptomic profiling of macrophages confirmed a highly dynamic signature during infection characterized by a switch from pro-inflammatory to anti-inflammatory/pro-regenerative status and revealed a shift in adhesion program. In agreement with this specific adhesion signature, macrophage trajectory tracking identifies motionless macrophages as a permissive niche for persistentSalmonella. Our results demonstrate that zebrafish model provides a unique platform to explore, in a whole organism, the versatile nature of macrophage functional programs during bacterial acute and persistent infections.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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