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Uropathogenic Escherichia coli Engages CD14-Dependent Signaling to Enable Bladder-Macrophage-Dependent Control of Acute Urinary Tract Infection
Journal article   Open access   Peer reviewed

Uropathogenic Escherichia coli Engages CD14-Dependent Signaling to Enable Bladder-Macrophage-Dependent Control of Acute Urinary Tract Infection

Alison J Carey, Matthew J Sullivan, Benjamin L Duell, David K Crossman, Debasish Chattopadhyay, Andrew J Brooks, Chee K Tan, Michael Crowley, Matthew J Sweet, Mark A Schembri, …
The Journal of infectious diseases, v 213(4), pp 659-668
15 Feb 2016
DOI: https://doi.org/10.1093/infdis/jiv424
PMID: 26324782
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://academic.oup.com/jid/article-pdf/213/4/659/17410674/jiv424.pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1093/infdis/jiv424View
Published, Version of Record (VoR) Open

Abstract

Animals Female Gene Deletion Gene Expression Profiling Lipopolysaccharide Receptors - genetics Lipopolysaccharide Receptors - metabolism Macrophages - immunology Mice, Inbred C57BL Mice, Knockout Signal Transduction Urinary Bladder - immunology Urinary Tract Infections - immunology Urinary Tract Infections - microbiology Uropathogenic Escherichia coli - immunology
CD14, a coreceptor for several pattern recognition receptors and a widely used monocyte/macrophage marker, plays a key role in host responses to gram-negative bacteria. Despite the central role of CD14 in the inflammatory response to lipopolysaccharide and other microbial products and in the dissemination of bacteria in some infections, the signaling networks controlled by CD14 during urinary tract infection (UTI) are unknown. We used uropathogenic Escherichia coli (UPEC) infection of wild-type (WT) C57BL/6 and Cd14(-/-) mice and RNA sequencing to define the CD14-dependent transcriptional signature and the role of CD14 in host defense against UTI in the bladder. UPEC induced the upregulation of Cd14 and the monocyte/macrophage-related genes Emr1/F4/80 and Csf1r/c-fms, which was associated with lower UPEC burdens in WT mice, compared with Cd14(-/-) mice. Exacerbation of infection in Cd14(-/-) mice was associated with the absence of a 491-gene transcriptional signature in the bladder that encompassed multiple host networks not previously associated with this receptor. CD14-dependent pathways included immune cell trafficking, differential cytokine production in macrophages, and interleukin 17 signaling. Depletion of monocytes/macrophages in the bladder by administration of liposomal clodronate led to higher UPEC burdens. This study identifies new host protective and signaling roles for CD14 in the bladder during UPEC UTI.

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35 citations in Web of Science
36 citations in Scopus

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Immunology
Infectious Diseases
Microbiology
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