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Spatial proteomics revealed a CX 3 CL1-dependent crosstalk between the urothelium and relocated macrophages through IL-6 during an acute bacterial infection in the urinary bladder.
- Source :
-
Mucosal immunology [Mucosal Immunol] 2020 Jul; Vol. 13 (4), pp. 702-714. Date of Electronic Publication: 2020 Feb 28. - Publication Year :
- 2020
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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 CX <subscript>3</subscript> CL1 was reduced in the urothelium. Accordingly, macrophage migration into the urothelium was diminished in the absence of CX <subscript>3</subscript> CL1 signaling in Cx <subscript>3</subscript> cr1 <superscript>gfp/gfp</superscript> mice. Conclusively, this study describes the crosstalk between the infected urothelium and macrophages through IL-6-induced CX <subscript>3</subscript> CL1 expression. Such crosstalk facilitates the relocation of macrophages into the urothelium and reduces bacterial burden in the urinary bladder.
- Subjects :
- Animals
Disease Models, Animal
Disease Susceptibility
Fluorescent Antibody Technique
Immunohistochemistry
Macrophages immunology
Mice
Urinary Bladder immunology
Urinary Bladder metabolism
Urinary Bladder microbiology
Urinary Tract Infections etiology
Urinary Tract Infections metabolism
Urinary Tract Infections pathology
Urothelium microbiology
Cell Communication
Chemokine CX3CL1 metabolism
Interleukin-6 metabolism
Macrophages metabolism
Proteomics methods
Urothelium immunology
Urothelium metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1935-3456
- Volume :
- 13
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Mucosal immunology
- Publication Type :
- Academic Journal
- Accession number :
- 32112048
- Full Text :
- https://doi.org/10.1038/s41385-020-0269-7