Advanced

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:
author
organization
publishing date
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
2007-07-25 10:39:33
date last changed
2016-10-13 04:23:29
@misc{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    = {ARRAY(0x8297818)},
  series       = {Journal of Immunology},
  title        = {Interaction with C4b-binding protein contributes to nontypeable Haemophilus influenzae serum resistance.},
  volume       = {178},
  year         = {2007},
}