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bioRxiv · 10.1101/2023.05.09.539693

Dynamics of macrophage polarization support Salmonella persistence in a whole living organism

Leiba, J.·Sipka, T.·Begon-Pescia, C.·Bernardello, M.·Tairi, S.·Bossi, L.·Gonzalez, A.-A.·Mialhe, X.·Gualda, E.·Loza-Alvarez, P.·Blanc-Potard, A.·Lutfalla, G.·Nguyen-Chi, M.
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Abstract

Numerous 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 persistent Salmonella Typhimurium 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, Salmonella persists 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 persistent Salmonella. 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.

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Leiba, J., Sipka, T., Begon-Pescia, C., Bernardello, M., Tairi, S., Bossi, L., Gonzalez, A.-A., Mialhe, X., Gualda, E., Loza-Alvarez, P., Blanc-Potard, A., Lutfalla, G., Nguyen-Chi, M.. 2023-05-10. Dynamics of macrophage polarization support Salmonella persistence in a whole living organism. https://doi.org/10.1101/2023.05.09.539693

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