Host response during unresolved urinary tract infection alters female mammary tissue homeostasis through collagen deposition and TIMP1

Henry, Samantha, Lewis, Steven Macauley, Cyrill, Samantha Leeanne, Callaway, Mackenzie Kate, Chatterjee, Deeptiman, Hanasoge Somasundara, Amritha Varshini, Jones, Gina, He, Xue-Yan, Caligiuri, Giuseppina, Ciccone, Michael Francis, Diaz, Isabella Andrea, Biswas, Amelia Aumalika, Hernandez, Evelyn, Ha, Taehoon, Wilkinson, John Erby, Egeblad, Mikala, Tuveson, David Arthur, Dos Santos, Camila Oresco (April 2024) Host response during unresolved urinary tract infection alters female mammary tissue homeostasis through collagen deposition and TIMP1. Nature Communications, 15 (1). p. 3282. ISSN 2041-1723 (Public Dataset)

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Abstract

Exposure to pathogens throughout a lifetime influences immunity and organ function. Here, we explore how the systemic host-response to bacterial urinary tract infection (UTI) induces tissue-specific alterations to the mammary gland. Utilizing a combination of histological tissue analysis, single cell transcriptomics, and flow cytometry, we identify that mammary tissue from UTI-bearing mice displays collagen deposition, enlarged ductal structures, ductal hyperplasia with atypical epithelial transcriptomes and altered immune composition. Bacterial cells are absent in the mammary tissue and blood of UTI-bearing mice, therefore, alterations to the distal mammary tissue are mediated by the systemic host response to local infection. Furthermore, broad spectrum antibiotic treatment resolves the infection and restores mammary cellular and tissue homeostasis. Systemically, unresolved UTI correlates with increased plasma levels of the metalloproteinase inhibitor, TIMP1, which controls extracellular matrix remodeling and neutrophil function. Treatment of nulliparous and post-lactation UTI-bearing female mice with a TIMP1 neutralizing antibody, restores mammary tissue normal homeostasis, thus providing evidence for a link between the systemic host response during UTI and mammary gland alterations.

Item Type:	Paper
Subjects:	organism description > animal organs, tissues, organelles, cell types and functions > tissues types and functions > mammary gland organism description > animal > mammal organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions organism description > animal > mammal > rodent organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:	Henry, Samantha Cyrill, Samantha L Caligiuri, Giuseppina Ciccone, Michael F Ha, Taehoon Egeblad, Mikala Tuveson, David A. Dos Santos, Camila O. Lewis, Steven M. Callaway, Mackenzie K. Chatterjee, Deeptiman Hanasoge Somasundara, Amritha Varshini Diaz, Isabella
Communities:	CSHL Cancer Center Program > Cancer Genetics and Genomics Program CSHL Cancer Center Program > Cellular Communication in Cancer Program CSHL labs > Dos Santos lab CSHL labs > Egeblad lab CSHL labs > Kinney lab CSHL labs > Tuveson lab CSHL Cancer Center Program
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	16 April 2024
Date Deposited:	18 Apr 2024 13:15
Last Modified:	18 Apr 2024 13:15
PMCID:	PMC11021735
Related URLs:	Publisher
Dataset ID:	BioProject: PRJNA855880 BioProject: PRJNA677888 https://github.com/dosSantosLabCSHL/scRNA-NP-P-UTI-SC-2022
URI:	https://repository.cshl.edu/id/eprint/41515

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