IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-47462-7.html
   My bibliography  Save this article

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

Author

Listed:
  • Samantha Henry

    (Cold Spring Harbor Laboratory
    Graduate Program in Genetics)

  • Steven Macauley Lewis

    (Cold Spring Harbor Laboratory
    Graduate Program in Genetics)

  • Samantha Leeanne Cyrill

    (Cold Spring Harbor Laboratory)

  • Mackenzie Kate Callaway

    (Cold Spring Harbor Laboratory)

  • Deeptiman Chatterjee

    (Cold Spring Harbor Laboratory)

  • Amritha Varshini Hanasoge Somasundara

    (Cold Spring Harbor Laboratory
    CSHL School of Biological Sciences)

  • Gina Jones

    (Cold Spring Harbor Laboratory)

  • Xue-Yan He

    (Department of Cell Biology and Physiology. School of Medicine in St. Louis. Washington University)

  • Giuseppina Caligiuri

    (Cold Spring Harbor Laboratory)

  • Michael Francis Ciccone

    (Cold Spring Harbor Laboratory)

  • Isabella Andrea Diaz

    (Cold Spring Harbor Laboratory)

  • Amelia Aumalika Biswas

    (Cold Spring Harbor Laboratory
    Neural and Behavior Science)

  • Evelyn Hernandez

    (Cold Spring Harbor Laboratory)

  • Taehoon Ha

    (Cold Spring Harbor Laboratory)

  • John Erby Wilkinson

    (University of Washington)

  • Mikala Egeblad

    (Department of Cell Biology, Department of Oncology, School of Medicine, Johns Hopkins University)

  • David Arthur Tuveson

    (Cold Spring Harbor Laboratory)

  • Camila Oresco dos Santos

    (Cold Spring Harbor Laboratory)

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.

Suggested Citation

  • Samantha Henry & Steven Macauley Lewis & Samantha Leeanne Cyrill & Mackenzie Kate Callaway & Deeptiman Chatterjee & Amritha Varshini Hanasoge Somasundara & Gina Jones & Xue-Yan He & Giuseppina Caligiu, 2024. "Host response during unresolved urinary tract infection alters female mammary tissue homeostasis through collagen deposition and TIMP1," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47462-7
    DOI: 10.1038/s41467-024-47462-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-47462-7
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-47462-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Suoqin Jin & Christian F. Guerrero-Juarez & Lihua Zhang & Ivan Chang & Raul Ramos & Chen-Hsiang Kuan & Peggy Myung & Maksim V. Plikus & Qing Nie, 2021. "Inference and analysis of cell-cell communication using CellChat," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    2. Michael Bartoschek & Nikolay Oskolkov & Matteo Bocci & John Lövrot & Christer Larsson & Mikael Sommarin & Chris D. Madsen & David Lindgren & Gyula Pekar & Göran Karlsson & Markus Ringnér & Jonas Bergh, 2018. "Spatially and functionally distinct subclasses of breast cancer-associated fibroblasts revealed by single cell RNA sequencing," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Hugo Croizer & Rana Mhaidly & Yann Kieffer & Geraldine Gentric & Lounes Djerroudi & Renaud Leclere & Floriane Pelon & Catherine Robley & Mylene Bohec & Arnaud Meng & Didier Meseure & Emanuela Romano &, 2024. "Deciphering the spatial landscape and plasticity of immunosuppressive fibroblasts in breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-28, December.
    2. Marina T. Broz & Emily Y. Ko & Kristin Ishaya & Jinfen Xiao & Marco Simone & Xen Ping Hoi & Roberta Piras & Basia Gala & Fernando H. G. Tessaro & Anja Karlstaedt & Sandra Orsulic & Amanda W. Lund & Ke, 2024. "Metabolic targeting of cancer associated fibroblasts overcomes T-cell exclusion and chemoresistance in soft-tissue sarcomas," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Sabrina Schütz & Llorenç Solé-Boldo & Carlota Lucena-Porcel & Jochen Hoffmann & Alexander Brobeil & Anke S. Lonsdorf & Manuel Rodríguez-Paredes & Frank Lyko, 2023. "Functionally distinct cancer-associated fibroblast subpopulations establish a tumor promoting environment in squamous cell carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Yanchuan Li & Huamei Li & Cheng Peng & Ge Meng & Yijun Lu & Honglin Liu & Li Cui & Huan Zhou & Zhu Xu & Lingyun Sun & Lihong Liu & Qing Xiong & Beicheng Sun & Shiping Jiao, 2024. "Unraveling the spatial organization and development of human thymocytes through integration of spatial transcriptomics and single-cell multi-omics profiling," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    5. Lichun Ma & Sophia Heinrich & Limin Wang & Friederike L. Keggenhoff & Subreen Khatib & Marshonna Forgues & Michael Kelly & Stephen M. Hewitt & Areeba Saif & Jonathan M. Hernandez & Donna Mabry & Roman, 2022. "Multiregional single-cell dissection of tumor and immune cells reveals stable lock-and-key features in liver cancer," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    6. Qingnan Liang & Yuefan Huang & Shan He & Ken Chen, 2023. "Pathway centric analysis for single-cell RNA-seq and spatial transcriptomics data with GSDensity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Faith H. Brennan & Yang Li & Cankun Wang & Anjun Ma & Qi Guo & Yi Li & Nicole Pukos & Warren A. Campbell & Kristina G. Witcher & Zhen Guan & Kristina A. Kigerl & Jodie C. E. Hall & Jonathan P. Godbout, 2022. "Microglia coordinate cellular interactions during spinal cord repair in mice," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    8. Sandra Curras-Alonso & Juliette Soulier & Thomas Defard & Christian Weber & Sophie Heinrich & Hugo Laporte & Sophie Leboucher & Sonia Lameiras & Marie Dutreix & Vincent Favaudon & Florian Massip & Tho, 2023. "An interactive murine single-cell atlas of the lung responses to radiation injury," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    9. Moujtaba Y. Kasmani & Paytsar Topchyan & Ashley K. Brown & Ryan J. Brown & Xiaopeng Wu & Yao Chen & Achia Khatun & Donia Alson & Yue Wu & Robert Burns & Chien-Wei Lin & Matthew R. Kudek & Jie Sun & We, 2023. "A spatial sequencing atlas of age-induced changes in the lung during influenza infection," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    10. Wei Yang & Li-Bo Liu & Feng-Liang Liu & Yan-Hua Wu & Zi-Da Zhen & Dong-Ying Fan & Zi-Yang Sheng & Zheng-Ran Song & Jia-Tong Chang & Yong-Tang Zheng & Jing An & Pei-Gang Wang, 2023. "Single-cell RNA sequencing reveals the fragility of male spermatogenic cells to Zika virus-induced complement activation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. Luke Simpson & Andrew Strange & Doris Klisch & Sophie Kraunsoe & Takuya Azami & Daniel Goszczynski & Triet Minh & Benjamin Planells & Nadine Holmes & Fei Sang & Sonal Henson & Matthew Loose & Jennifer, 2024. "A single-cell atlas of pig gastrulation as a resource for comparative embryology," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    12. Xiaojian Lu & Yanwei Luo & Xichen Nie & Bailing Zhang & Xiaoyan Wang & Ran Li & Guangmin Liu & Qianyin Zhou & Zhizhong Liu & Liqing Fan & James M. Hotaling & Zhe Zhang & Hao Bo & Jingtao Guo, 2023. "Single-cell multi-omics analysis of human testicular germ cell tumor reveals its molecular features and microenvironment," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    13. Anjun Ma & Xiaoying Wang & Jingxian Li & Cankun Wang & Tong Xiao & Yuntao Liu & Hao Cheng & Juexin Wang & Yang Li & Yuzhou Chang & Jinpu Li & Duolin Wang & Yuexu Jiang & Li Su & Gang Xin & Shaopeng Gu, 2023. "Single-cell biological network inference using a heterogeneous graph transformer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    14. Jeff DeMartino & Michael T. Meister & Lindy L. Visser & Mariël Brok & Marian J. A. Groot Koerkamp & Amber K. L. Wezenaar & Laura S. Hiemcke-Jiwa & Terezinha Souza & Johannes H. M. Merks & Anne C. Rios, 2023. "Single-cell transcriptomics reveals immune suppression and cell states predictive of patient outcomes in rhabdomyosarcoma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    15. Zi-Xun Yan & Yan Dong & Niu Qiao & Yi-Lun Zhang & Wen Wu & Yue Zhu & Li Wang & Shu Cheng & Peng-Peng Xu & Zi-Song Zhou & Ling-Shuang Sheng & Wei-Li Zhao, 2024. "Cholesterol efflux from C1QB-expressing macrophages is associated with resistance to chimeric antigen receptor T cell therapy in primary refractory diffuse large B cell lymphoma," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    16. Junjun Jing & Jifan Feng & Yuan Yuan & Tingwei Guo & Jie Lei & Fei Pei & Thach-Vu Ho & Yang Chai, 2022. "Spatiotemporal single-cell regulatory atlas reveals neural crest lineage diversification and cellular function during tooth morphogenesis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    17. Daniel Dimitrov & Dénes Türei & Martin Garrido-Rodriguez & Paul L. Burmedi & James S. Nagai & Charlotte Boys & Ricardo O. Ramirez Flores & Hyojin Kim & Bence Szalai & Ivan G. Costa & Alberto Valdeoliv, 2022. "Comparison of methods and resources for cell-cell communication inference from single-cell RNA-Seq data," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    18. Xi Li & Alfonso Poire & Kang Jin Jeong & Dong Zhang & Tugba Yildiran Ozmen & Gang Chen & Chaoyang Sun & Gordon B. Mills, 2024. "C5aR1 inhibition reprograms tumor associated macrophages and reverses PARP inhibitor resistance in breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    19. Nunya Chotiwan & Ebba Rosendal & Stefanie M. A. Willekens & Erin Schexnaydre & Emma Nilsson & Richard Lindqvist & Max Hahn & Ionut Sebastian Mihai & Federico Morini & Jianguo Zhang & Gregory D. Ebel &, 2023. "Type I interferon shapes brain distribution and tropism of tick-borne flavivirus," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    20. Vishnu Muraleedharan Saraswathy & Lili Zhou & Mayssa H. Mokalled, 2024. "Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47462-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.