Host response during unresolved urinary tract infection alters 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, Hernandez, Evelyn, Ha, Taehoon, Wilkinson, John Erby, Egeblad, Mikala, Tuveson, David Arthur, Oresco dos Santos, Camila (February 2024) Host response during unresolved urinary tract infection alters mammary tissue homeostasis through collagen deposition and TIMP1. bioRxiv. (Public Dataset) (Submitted)

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DOI: 10.1101/2024.02.05.578977


Exposure to pathogens throughout a lifetime influences immunity and organ function. Here, we explored 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 RNA sequencing and flow cytometry, we identified that mammary tissue from UTI-bearing mice display collagen deposition, enlarged ductal structures, ductal hyperplasia with atypical epithelial transcriptomes and altered immune composition. Bacterial cells were absent in the mammary tissue and blood of UTI-bearing mice, therefore, alterations to the distal mammary tissue were mediated by the systemic host response to local infection. Furthermore, broad spectrum antibiotic treatment resolved the infection and restored mammary cellular and tissue homeostasis. Systemically, unresolved UTI correlated with increased plasma levels of the metalloproteinase inhibitor, TIMP1, which controls extracellular matrix (ECM) remodeling and neutrophil function. Treatment of nulliparous and post-lactation UTI-bearing female mice with a TIMP1 neutralizing antibody, or broad-spectrum antibiotic, prevented mammary collagen deposition, thus providing evidence for an unexpected link between the systemic host response during UTI and mammary alterations.

Item Type: Paper
Subjects: diseases & disorders > Bacterial Infections
diseases & disorders
CSHL Authors:
Communities: CSHL Cancer Center Shared Resources
CSHL labs > Dos Santos lab
CSHL labs > Egeblad lab
CSHL labs > Kinney lab
CSHL labs > Tuveson lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 6 February 2024
Date Deposited: 20 Mar 2024 13:16
Last Modified: 29 Apr 2024 15:35
Related URLs:
Dataset ID:
  • BioProject: SUB11741283
  • BioProject: SUB8429356

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