Relocation of macrophages maintains the barrier function of the urothelium and protects against persistent infection

Bottek, J.; Soun, C.; Volke, J. K.; Dixit, A.; Thiebes, S.; Beerlage, A.-L.; Horstmann, M.; Urbanek, A.; Uszkoreit, J.; Eisenacher, M.; Bracht, T.; Sitek, B.; Hoffmann, F.; Vijitha, N.; von Eggeling, F.; Engel, D. R.

doi:10.1101/649137

bioRxiv · 10.1101/649137

Relocation of macrophages maintains the barrier function of the urothelium and protects against persistent infection

Bottek, J.·Soun, C.·Volke, J. K.·Dixit, A.·Thiebes, S.·Beerlage, A.-L.·Horstmann, M.·Urbanek, A.·Uszkoreit, J.·Eisenacher, M.·Bracht, T.·Sitek, B.·Hoffmann, F.·Vijitha, N.·von Eggeling, F.·Engel, D. R.

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Abstract

Macrophages perform essential functions during bacterial infections, such as phagocytosis of pathogens and elimination of neutrophils to reduce spreading of infection, inflammation and tissue damage. The spatial distribution of macrophages is critical to respond to tissue specific adaptations upon infections. Using a novel algorithm for correlative mass spectrometry imaging and state-of-the-art multiplex microscopy, we report here that macrophages within the urinary bladder are positioned in the connective tissue underneath the urothelium. Invading uropathogenic E.coli induced an IL-6-dependent CX3CL1 expression by urothelial cells, facilitating relocation of macrophages from the connective tissue into the urothelium. These cells phagocytosed UPECs and eliminated neutrophils to maintain barrier function of the urothelium, preventing persistent and recurrent urinary tract infection. O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY GRAPHICAL ABSTRACT C_FIG_DISPLAY

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Bottek, J., Soun, C., Volke, J. K., Dixit, A., Thiebes, S., Beerlage, A.-L., Horstmann, M., Urbanek, A., Uszkoreit, J., Eisenacher, M., Bracht, T., Sitek, B., Hoffmann, F., Vijitha, N., von Eggeling, F., Engel, D. R.. 2019-06-06. Relocation of macrophages maintains the barrier function of the urothelium and protects against persistent infection. https://doi.org/10.1101/649137

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