Enterococcus faecalis Escapes Complement-Mediated Killing via Recruitment of Complement Factor H.
Animals
Antibodies, Bacterial
/ blood
Complement C3b
/ immunology
Complement C4b
/ immunology
Complement Factor H
/ immunology
Complement Pathway, Mannose-Binding Lectin
/ immunology
Complement System Proteins
/ immunology
Disease Models, Animal
Enterococcus faecalis
/ immunology
Gram-Positive Bacterial Infections
/ immunology
Humans
Lectins
Mice
Mice, Inbred BALB C
Peritonitis
/ immunology
Phagocytosis
/ immunology
Ficolins
Enterococcus faecalis
Factor H
complement system
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
09 08 2019
09 08 2019
Historique:
received:
25
03
2019
accepted:
01
05
2019
pubmed:
7
5
2019
medline:
21
5
2020
entrez:
7
5
2019
Statut:
ppublish
Résumé
Enterococcus faecalis is considered to be the most important species of enterococci responsible for blood stream infections in critically ill patients. In blood, the complement system is activated via the classical pathway (CP), the lectin pathway (LP), or the alternative pathway (AP), and it plays a critical role in opsonophagocytosis of bacteria including E faecalis. In a mouse model of enterococcus peritonitis, BALB-C mice were challenged with a high dose of E faecalis 12 hours after intraperitoneal administration of anti-Factor H (FH) antibodies or isotype control. Four hours later, control mice developed higher bacterial burden in blood and organs compared with mice treated with anti-FH antibodies. We demonstrate that complement recognition molecules C1q, CL-11, and murine ficolin-A bind the enterococcus and drive the CP and the LP in human and mouse. We further describe that E faecalis evades the AP by recruitment of FH on its surface. Our results show a strong C3b deposition on E faecalis via both the CP and the LP but not through the AP. These findings indicate that E faecalis avoids the complement phagocytosis by the AP via sequestering complement FH from the host blood.
Sections du résumé
BACKGROUND
Enterococcus faecalis is considered to be the most important species of enterococci responsible for blood stream infections in critically ill patients. In blood, the complement system is activated via the classical pathway (CP), the lectin pathway (LP), or the alternative pathway (AP), and it plays a critical role in opsonophagocytosis of bacteria including E faecalis.
METHODS
In a mouse model of enterococcus peritonitis, BALB-C mice were challenged with a high dose of E faecalis 12 hours after intraperitoneal administration of anti-Factor H (FH) antibodies or isotype control. Four hours later, control mice developed higher bacterial burden in blood and organs compared with mice treated with anti-FH antibodies.
RESULTS
We demonstrate that complement recognition molecules C1q, CL-11, and murine ficolin-A bind the enterococcus and drive the CP and the LP in human and mouse. We further describe that E faecalis evades the AP by recruitment of FH on its surface. Our results show a strong C3b deposition on E faecalis via both the CP and the LP but not through the AP.
CONCLUSIONS
These findings indicate that E faecalis avoids the complement phagocytosis by the AP via sequestering complement FH from the host blood.
Identifiants
pubmed: 31058287
pii: 5485924
doi: 10.1093/infdis/jiz226
doi:
Substances chimiques
Antibodies, Bacterial
0
Lectins
0
Complement C3b
80295-43-8
Complement C4b
80295-50-7
Complement Factor H
80295-65-4
Complement System Proteins
9007-36-7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1061-1070Subventions
Organisme : Medical Research Council
ID : G0700859
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0801952
Pays : United Kingdom
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.