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. and Ulett, Glen C. (2015) Uropathogenic Escherichia coli engages CD14-dependent signaling to enable bladder macrophage-dependent control of acute urinary tract infection. The Journal of infectious diseases, 213 4: 659-668. doi:10.1093/infdis/jiv424


Author 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.
Title Uropathogenic Escherichia coli engages CD14-dependent signaling to enable bladder macrophage-dependent control of acute urinary tract infection
Journal name The Journal of infectious diseases   Check publisher's open access policy
ISSN 1537-6613
0022-1899
Publication date 2015-09-22
Year available 2015
Sub-type Article (original research)
DOI 10.1093/infdis/jiv424
Open Access Status Not Open Access
Volume 213
Issue 4
Start page 659
End page 668
Total pages 11
Place of publication Cary, North Carolina, United States
Publisher Oxford University Press
Collection year 2016
Language eng
Formatted 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.

Conclusion. This study identifies new host protective and signaling roles for CD14 in the bladder during UPEC UTI.
Keyword Urinary tract infection
Urpathogenic Escherichia coli
Host response
CD14
RNA sequencing
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Mon, 12 Oct 2015, 14:34:42 EST by Andrew Brooks on behalf of Institute for Molecular Bioscience