AI Article Synopsis
- The urothelium is a protective layer in the bladder, but harmful bacteria like E. coli can damage it, leading to infections.
- This study shows that certain immune cells called macrophages move into the urothelium to help fight these infections.
- They found that a protein called IL-6 helps send signals for macrophages to migrate, and without it, the infection gets worse because fewer macrophages can get to the area.
Article Abstract
The urothelium of the urinary bladder represents the first line of defense. However, uropathogenic E. coli (UPEC) damage the urothelium and cause acute bacterial infection. Here, we demonstrate the crosstalk between macrophages and the urothelium stimulating macrophage migration into the urothelium. Using spatial proteomics by MALDI-MSI and LC-MS/MS, a novel algorithm revealed the spatial activation and migration of macrophages. Analysis of the spatial proteome unravelled the coexpression of Myo9b and F4/80 in the infected urothelium, indicating that macrophages have entered the urothelium upon infection. Immunofluorescence microscopy additionally indicated that intraurothelial macrophages phagocytosed UPEC and eliminated neutrophils. Further analysis of the spatial proteome by MALDI-MSI showed strong expression of IL-6 in the urothelium and local inhibition of this molecule reduced macrophage migration into the urothelium and aggravated the infection. After IL-6 inhibition, the expression of matrix metalloproteinases and chemokines, such as CXCL1 was reduced in the urothelium. Accordingly, macrophage migration into the urothelium was diminished in the absence of CXCL1 signaling in Cxcr1 mice. Conclusively, this study describes the crosstalk between the infected urothelium and macrophages through IL-6-induced CXCL1 expression. Such crosstalk facilitates the relocation of macrophages into the urothelium and reduces bacterial burden in the urinary bladder.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312419 | PMC |
| http://dx.doi.org/10.1038/s41385-020-0269-7 | DOI Listing |
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