Uropathogenic Escherichia coli engages CD14-dependent signaling to enable bladder macrophage-dependent control of acute urinary tract infection
File version
Accepted Manuscript (AM)
Author(s)
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
Griffith University Author(s)
Primary Supervisor
Other Supervisors
Editor(s)
Date
Size
File type(s)
Location
License
Abstract
INTRODUCTION: CD14, a co-receptor for several pattern recognition receptors and a widely used monocyte/macrophage marker, plays a key role in host responses to Gram-negative bacteria. Despite its central role in the inflammatory response to lipopolysaccharide and other microbial products, and in 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-deficient mice and RNA-sequencing (RNA-seq) to define the CD14-dependent transcriptional signature, and role of CD14, in host defense against UTI in the bladder. RESULTS: UPEC-induced the up-regulation of Cd14 and monocyte/macrophage related genes Emr1/F4/80 and Csf1r/c-fms, which was associated with lower UPEC burdens in WT compared to Cd14-deficient mice. Exacerbation of infection in Cd14-deficient 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 IL-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.
Journal Title
The Journal of Infectious Diseases
Conference Title
Book Title
Edition
Volume
213
Issue
4
Thesis Type
Degree Program
School
Publisher link
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement
© 2016 by Oxford University Press This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Journal of Infectious Diseases following peer review. The definitive publisher-authenticated version, Uropathogenic Escherichia coli engages CD14-dependent signaling to enable bladder macrophage-dependent control of acute urinary tract infection, Journal of Infectious Diseases, Vol. 213 (4), pp. 659-668, is available online at: http://dx.doi.org/10.1093/infdis/jiv424.
Item Access Status
Note
Access the data
Related item(s)
Subject
Biological sciences
Biomedical and clinical sciences
Medical bacteriology