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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, Ben LU ; Crossman, David K.; Chattopadhyay, Debasish; Brooks, Andrew J.; Tan, Chee K.; Crowley, Michael; Sweet, Matthew J. and Schembri, Mark A., et al. (2016) In Journal of Infectious Diseases 213(4). p.659-668
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... (More)

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.

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organization
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Contribution to journal
publication status
published
subject
keywords
CD14, host response, RNA sequencing, urinary tract infection, uropathogenic Escherichia coli
in
Journal of Infectious Diseases
volume
213
issue
4
pages
10 pages
publisher
Oxford University Press
external identifiers
  • Scopus:84960192430
  • WOS:000372437700024
ISSN
0022-1899
DOI
10.1093/infdis/jiv424
language
English
LU publication?
yes
id
af95a283-e349-48c6-b90a-9f5d32be6a27
date added to LUP
2016-05-13 15:27:15
date last changed
2016-11-06 04:37:50
@misc{af95a283-e349-48c6-b90a-9f5d32be6a27,
  abstract     = {<p>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<sup>-/-</sup> 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<sup>-/-</sup> mice. Exacerbation of infection in Cd14<sup>-/-</sup> 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.</p>},
  author       = {Carey, Alison J. and Sullivan, Matthew J. and Duell, Ben and Crossman, David K. and Chattopadhyay, Debasish and Brooks, Andrew J. and Tan, Chee K. and Crowley, Michael and Sweet, Matthew J. and Schembri, Mark A. and Ulett, Glen C.},
  issn         = {0022-1899},
  keyword      = {CD14,host response,RNA sequencing,urinary tract infection,uropathogenic Escherichia coli},
  language     = {eng},
  number       = {4},
  pages        = {659--668},
  publisher    = {ARRAY(0x81b1088)},
  series       = {Journal of Infectious Diseases},
  title        = {Uropathogenic Escherichia coli engages CD14-dependent signaling to enable bladder-macrophage-dependent control of acute urinary tract infection},
  url          = {http://dx.doi.org/10.1093/infdis/jiv424},
  volume       = {213},
  year         = {2016},
}