Uropathogenic Escherichia Coli engages CD14-dependent signaling to enable bladder-macrophage-dependent control of acute urinary tract infection

Carey, Alison J., Sullivan, Matthew J., Duell, Benjamin L., Crossman, David K., Chattopadhyay, Debasish, Brooks, Andrew J., Tan, Chee K., Crowley, Michael, Sweet, Matthew J., Schembri, Mark A., & Ulett, Glen C. (2016) Uropathogenic Escherichia Coli engages CD14-dependent signaling to enable bladder-macrophage-dependent control of acute urinary tract infection. Journal of Infectious Diseases, 213(4), pp. 659-668.

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Abstract

Background

  • 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.

Methods

  • 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.

Results

  • 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.

Conclusions

  • This study identifies new host protective and signaling roles for CD14 in the bladder during UPEC UTI.

Impact and interest:

2 citations in Scopus
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5 citations in Web of Science®

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ID Code: 91395
Item Type: Journal Article
Refereed: Yes
Keywords: urinary tract infection, uropathogenic Escherichia coli, host response, CD14, RNA sequencing
DOI: 10.1093/infdis/jiv424
ISSN: 1537-6613
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > MICROBIOLOGY (060500) > Bacteriology (060501)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > IMMUNOLOGY (110700) > Innate Immunity (110707)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2015 The Author. Published by Oxford University Press on behalf of the Infectious Diseases Society of America
Deposited On: 17 Dec 2015 23:09
Last Modified: 02 Sep 2016 21:38

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