Enolase of Streptococcus pneumoniae Binds Human Complement Inhibitor C4b-Binding Protein and Contributes to Complement Evasion.
Agarwal, Vaibhav LU ; Hammerschmidt, Sven ; Malm, Sven ; Bergmann, Simone ; Riesbeck, Kristian LU
and Blom, Anna
LU
(2012)
In Journal of immunology
189(7).
p.3575-3584
- Abstract
- Streptococcus pneumoniae (pneumococcus) is a pathogen that causes severe local and life-threatening invasive diseases, which are associated with high mortality rates. Pneumococci have evolved several strategies to evade the host immune system, including complement to disseminate and to survive in various host niches. Thus, pneumococci bind complement inhibitors such as C4b-binding protein (C4BP) and factor H via pneumococcal surface protein C, thereby inhibiting the classical and alternative complement pathways. In this study, we identified the pneumococcal glycolytic enzyme enolase, a nonclassical cell surface and plasminogen-binding protein, as an additional pneumococcal C4BP-binding protein. Furthermore, we demonstrated that human, but... (More)
- Streptococcus pneumoniae (pneumococcus) is a pathogen that causes severe local and life-threatening invasive diseases, which are associated with high mortality rates. Pneumococci have evolved several strategies to evade the host immune system, including complement to disseminate and to survive in various host niches. Thus, pneumococci bind complement inhibitors such as C4b-binding protein (C4BP) and factor H via pneumococcal surface protein C, thereby inhibiting the classical and alternative complement pathways. In this study, we identified the pneumococcal glycolytic enzyme enolase, a nonclassical cell surface and plasminogen-binding protein, as an additional pneumococcal C4BP-binding protein. Furthermore, we demonstrated that human, but not mouse, C4BP bound pneumococci. Recombinant enolase bound in a dose-dependent manner C4BP purified from plasma, and the interaction was reduced by increasing ionic strength. Enolase recruited C4BP and plasminogen, but not factor H, from human serum. Moreover, C4BP and plasminogen bound to different domains of enolase as they did not compete for the interaction with enolase. In direct binding assays with recombinant C4BP mutants lacking individual domains, two binding sites for enolase were identified on the complement control protein (CCP) domain 1/CCP2 and CCP8 of the C4BP α-chains. C4BP bound to the enolase retained its cofactor activity as determined by C4b degradation. Furthermore, in the presence of exogenously added enolase, an increased C4BP binding to and subsequently decreased C3b deposition on pneumococci was observed. Taken together, pneumococci specifically interact with human C4BP via enolase, which represents an additional mechanism of human complement control by this versatile pathogen. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3047107
- author
- Agarwal, Vaibhav
LU
; Hammerschmidt, Sven
; Malm, Sven
; Bergmann, Simone
; Riesbeck, Kristian
LU
and Blom, Anna
LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of immunology
- volume
- 189
- issue
- 7
- pages
- 3575 - 3584
- publisher
- American Association of Immunologists
- external identifiers
-
- wos:000309164300034
- pmid:22925928
- scopus:84866554657
- pmid:22925928
- ISSN
- 1550-6606
- DOI
- 10.4049/jimmunol.1102934
- language
- English
- LU publication?
- yes
- id
- 08177fb1-107b-4410-8330-c6ae58db6f49 (old id 3047107)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22925928?dopt=Abstract
- date added to LUP
- 2016-04-04 09:39:45
- date last changed
- 2022-04-16 00:30:22
@article{08177fb1-107b-4410-8330-c6ae58db6f49,
abstract = {{Streptococcus pneumoniae (pneumococcus) is a pathogen that causes severe local and life-threatening invasive diseases, which are associated with high mortality rates. Pneumococci have evolved several strategies to evade the host immune system, including complement to disseminate and to survive in various host niches. Thus, pneumococci bind complement inhibitors such as C4b-binding protein (C4BP) and factor H via pneumococcal surface protein C, thereby inhibiting the classical and alternative complement pathways. In this study, we identified the pneumococcal glycolytic enzyme enolase, a nonclassical cell surface and plasminogen-binding protein, as an additional pneumococcal C4BP-binding protein. Furthermore, we demonstrated that human, but not mouse, C4BP bound pneumococci. Recombinant enolase bound in a dose-dependent manner C4BP purified from plasma, and the interaction was reduced by increasing ionic strength. Enolase recruited C4BP and plasminogen, but not factor H, from human serum. Moreover, C4BP and plasminogen bound to different domains of enolase as they did not compete for the interaction with enolase. In direct binding assays with recombinant C4BP mutants lacking individual domains, two binding sites for enolase were identified on the complement control protein (CCP) domain 1/CCP2 and CCP8 of the C4BP α-chains. C4BP bound to the enolase retained its cofactor activity as determined by C4b degradation. Furthermore, in the presence of exogenously added enolase, an increased C4BP binding to and subsequently decreased C3b deposition on pneumococci was observed. Taken together, pneumococci specifically interact with human C4BP via enolase, which represents an additional mechanism of human complement control by this versatile pathogen.}},
author = {{Agarwal, Vaibhav and Hammerschmidt, Sven and Malm, Sven and Bergmann, Simone and Riesbeck, Kristian and Blom, Anna}},
issn = {{1550-6606}},
language = {{eng}},
number = {{7}},
pages = {{3575--3584}},
publisher = {{American Association of Immunologists}},
series = {{Journal of immunology}},
title = {{Enolase of Streptococcus pneumoniae Binds Human Complement Inhibitor C4b-Binding Protein and Contributes to Complement Evasion.}},
url = {{http://dx.doi.org/10.4049/jimmunol.1102934}},
doi = {{10.4049/jimmunol.1102934}},
volume = {{189}},
year = {{2012}},
}