Interaction with C4b-binding protein contributes to nontypeable Haemophilus influenzae serum resistance.
Hallström, Teresia LU ; Jarva, Hanna LU ; Riesbeck, Kristian LU
and Blom, Anna
LU
(2007)
In Journal of Immunology
178(10).
p.6359-6366
- Abstract
- Complement evasion by various mechanisms is important for microbial virulence and survival in the host. One strategy used by some pathogenic bacteria is to bind the complement inhibitor of the classical pathway, C4b-binding protein (C4BP). In this study, we have identified a novel interaction between nontypeable Haemophilus influenzae (NTHi) and C4BP, whereas the majority of the typeable H. influenzae (a-f) tested showed no binding. One of the clinical isolates, NTHi 506, displayed a particularly high binding of C4BP and was used for detailed analysis of the interaction. Importantly, a low C4BP-binding isolate (NTHi 69) showed an increased deposition of C3b followed by reduced survival as compared with NTHi 506 when exposed to normal human... (More)
- Complement evasion by various mechanisms is important for microbial virulence and survival in the host. One strategy used by some pathogenic bacteria is to bind the complement inhibitor of the classical pathway, C4b-binding protein (C4BP). In this study, we have identified a novel interaction between nontypeable Haemophilus influenzae (NTHi) and C4BP, whereas the majority of the typeable H. influenzae (a-f) tested showed no binding. One of the clinical isolates, NTHi 506, displayed a particularly high binding of C4BP and was used for detailed analysis of the interaction. Importantly, a low C4BP-binding isolate (NTHi 69) showed an increased deposition of C3b followed by reduced survival as compared with NTHi 506 when exposed to normal human serum. The main isoform of C4BP contains seven identical a-chains and one beta-chain linked together with disulfide bridges. Each a-chain is composed of eight complement control protein (CCP) modules and we have found that the NTHi 506 strain did not interact with rC4BP lacking CCP2 or CCP7 showing that these two CCPs are important for the binding. Importantly, C4BP bound to the surface of H. influenzae retained its cofactor activity as determined by analysis of C3b and C4b degradation. Taken together, NTHi interferes with the classical complement activation pathway by binding to C4BP. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/168455
- author
- Hallström, Teresia
LU
; Jarva, Hanna
LU
; Riesbeck, Kristian
LU
and Blom, Anna
LU
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Immunology
- volume
- 178
- issue
- 10
- pages
- 6359 - 6366
- publisher
- American Association of Immunologists
- external identifiers
-
- wos:000246286200043
- scopus:34248228732
- ISSN
- 1550-6606
- language
- English
- LU publication?
- yes
- id
- e98fc65f-f641-4115-a7f2-0e28028cae7f (old id 168455)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17475865&dopt=Abstract
- date added to LUP
- 2016-04-04 09:04:37
- date last changed
- 2022-03-15 17:32:35
@article{e98fc65f-f641-4115-a7f2-0e28028cae7f,
abstract = {{Complement evasion by various mechanisms is important for microbial virulence and survival in the host. One strategy used by some pathogenic bacteria is to bind the complement inhibitor of the classical pathway, C4b-binding protein (C4BP). In this study, we have identified a novel interaction between nontypeable Haemophilus influenzae (NTHi) and C4BP, whereas the majority of the typeable H. influenzae (a-f) tested showed no binding. One of the clinical isolates, NTHi 506, displayed a particularly high binding of C4BP and was used for detailed analysis of the interaction. Importantly, a low C4BP-binding isolate (NTHi 69) showed an increased deposition of C3b followed by reduced survival as compared with NTHi 506 when exposed to normal human serum. The main isoform of C4BP contains seven identical a-chains and one beta-chain linked together with disulfide bridges. Each a-chain is composed of eight complement control protein (CCP) modules and we have found that the NTHi 506 strain did not interact with rC4BP lacking CCP2 or CCP7 showing that these two CCPs are important for the binding. Importantly, C4BP bound to the surface of H. influenzae retained its cofactor activity as determined by analysis of C3b and C4b degradation. Taken together, NTHi interferes with the classical complement activation pathway by binding to C4BP.}},
author = {{Hallström, Teresia and Jarva, Hanna and Riesbeck, Kristian and Blom, Anna}},
issn = {{1550-6606}},
language = {{eng}},
number = {{10}},
pages = {{6359--6366}},
publisher = {{American Association of Immunologists}},
series = {{Journal of Immunology}},
title = {{Interaction with C4b-binding protein contributes to nontypeable Haemophilus influenzae serum resistance.}},
url = {{http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17475865&dopt=Abstract}},
volume = {{178}},
year = {{2007}},
}