TY - JOUR
T1 - Enterococcus faecalis promotes innate immune suppression and polymicrobial catheterassociated urinary tract infection
AU - Tien, Brenda Yin Qi
AU - Goh, Hwee Mian Sharon
AU - Chong, Kelvin Kian Long
AU - Bhaduri-Tagore, Soumili
AU - Holec, Sarah
AU - Dress, Regine
AU - Ginhoux, Florent
AU - Ingersoll, Molly A.
AU - Williams, Rohan B.H.
AU - Kline, Kimberly A.
N1 - Publisher Copyright:
© 2017 American Society for Microbiology.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Enterococcus faecalis, a member of the human gastrointestinal microbiota, is an opportunistic pathogen associated with hospital-acquired wound, bloodstream, and urinary tract infections. E. faecalis can subvert or evade immunemediated clearance, although the mechanisms are poorly understood. In this study, we examined E. faecalis-mediated subversion of macrophage activation. We observed that E. faecalis actively prevents NF-κB signaling in mouse RAW264.7 macrophages in the presence of Toll-like receptor agonists and during polymicrobial infection with Escherichia coli. E. faecalis and E. coli coinfection in a mouse model of catheter-associated urinary tract infection (CAUTI) resulted in a suppressed macrophage transcriptional response in the bladder compared to that with E. coli infection alone. Finally, we demonstrated that coinoculation of E. faecalis with a commensal strain of E. coli into catheterized bladders significantly augmented E. coli CAUTI. Taken together, these results support the hypothesis that E. faecalis suppression of NF-κB-driven responses in macrophages promotes polymicrobial CAUTI pathogenesis, especially during coinfection with less virulent or commensal E. coli strains.
AB - Enterococcus faecalis, a member of the human gastrointestinal microbiota, is an opportunistic pathogen associated with hospital-acquired wound, bloodstream, and urinary tract infections. E. faecalis can subvert or evade immunemediated clearance, although the mechanisms are poorly understood. In this study, we examined E. faecalis-mediated subversion of macrophage activation. We observed that E. faecalis actively prevents NF-κB signaling in mouse RAW264.7 macrophages in the presence of Toll-like receptor agonists and during polymicrobial infection with Escherichia coli. E. faecalis and E. coli coinfection in a mouse model of catheter-associated urinary tract infection (CAUTI) resulted in a suppressed macrophage transcriptional response in the bladder compared to that with E. coli infection alone. Finally, we demonstrated that coinoculation of E. faecalis with a commensal strain of E. coli into catheterized bladders significantly augmented E. coli CAUTI. Taken together, these results support the hypothesis that E. faecalis suppression of NF-κB-driven responses in macrophages promotes polymicrobial CAUTI pathogenesis, especially during coinfection with less virulent or commensal E. coli strains.
KW - Catheter-associated UTI
KW - Coinfection
KW - Enterococcus faecalis
KW - Escherichia coli
KW - Immune suppression
KW - Macrophage
KW - Polymicrobial
KW - Urinary tract infection
UR - http://www.scopus.com/inward/record.url?scp=85034093470&partnerID=8YFLogxK
U2 - 10.1128/IAI.00378-17
DO - 10.1128/IAI.00378-17
M3 - Article
C2 - 28893918
AN - SCOPUS:85034093470
SN - 0019-9567
VL - 85
JO - Infection and Immunity
JF - Infection and Immunity
IS - 12
M1 - e00378-17
ER -