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Immune Evasion of Moraxella catarrhalis Involves Ubiquitous Surface Protein A-Dependent C3d Binding.

Hallström, Teresia LU ; Nordström, Therése LU ; Tan, Thuan Tong; Manolov, Taras; Lambris, John D; Isenman, David E; Zipfel, Peter F; Blom, Anna LU and Riesbeck, Kristian LU (2011) In Journal of immunology (Baltimore, Md. : 1950) 186. p.3120-3129
Abstract
The complement system plays an important role in eliminating invading pathogens. Activation of complement results in C3b deposition (opsonization), phagocytosis, anaphylatoxin (C3a, C5a) release, and consequently cell lysis. Moraxella catarrhalis is a human respiratory pathogen commonly found in children with otitis media and in adults with chronic obstructive pulmonary disease. The species has evolved multiple complement evasion strategies, which among others involves the ubiquitous surface protein (Usp) family consisting of UspA1, A2, and A2 hybrid. In the present study, we found that the ability of M. catarrhalis to bind C3 correlated with UspA expression and that C3 binding contributed to serum resistance in a large number of clinical... (More)
The complement system plays an important role in eliminating invading pathogens. Activation of complement results in C3b deposition (opsonization), phagocytosis, anaphylatoxin (C3a, C5a) release, and consequently cell lysis. Moraxella catarrhalis is a human respiratory pathogen commonly found in children with otitis media and in adults with chronic obstructive pulmonary disease. The species has evolved multiple complement evasion strategies, which among others involves the ubiquitous surface protein (Usp) family consisting of UspA1, A2, and A2 hybrid. In the present study, we found that the ability of M. catarrhalis to bind C3 correlated with UspA expression and that C3 binding contributed to serum resistance in a large number of clinical isolates. Recombinantly expressed UspA1 and A2 inhibit both the alternative and classical pathways, C3b deposition, and C3a generation when bound to the C3 molecule. We also revealed that the M. catarrhalis UspA-binding domain on C3b was located to C3d and that the major bacterial C3d-binding domains were within UspA1(299-452) and UspA2(165-318). The interaction with C3 was not species specific since UspA-expressing M. catarrhalis also bound mouse C3 that resulted in inhibition of the alternative pathway of mouse complement. Taken together, the binding of C3 to UspAs is an efficient strategy of Moraxella to block the activation of complement and to inhibit C3a-mediated inflammation. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of immunology (Baltimore, Md. : 1950)
volume
186
pages
3120 - 3129
publisher
American Association of Immunologists
external identifiers
  • WOS:000287356900050
  • PMID:21270401
  • Scopus:79952773851
ISSN
1550-6606
DOI
10.4049/jimmunol.1002621
language
English
LU publication?
yes
id
80fa2c5f-c683-4f50-8a7a-c533bb3da9c5 (old id 1777037)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21270401?dopt=Abstract
date added to LUP
2011-02-01 09:35:02
date last changed
2016-11-01 10:16:42
@misc{80fa2c5f-c683-4f50-8a7a-c533bb3da9c5,
  abstract     = {The complement system plays an important role in eliminating invading pathogens. Activation of complement results in C3b deposition (opsonization), phagocytosis, anaphylatoxin (C3a, C5a) release, and consequently cell lysis. Moraxella catarrhalis is a human respiratory pathogen commonly found in children with otitis media and in adults with chronic obstructive pulmonary disease. The species has evolved multiple complement evasion strategies, which among others involves the ubiquitous surface protein (Usp) family consisting of UspA1, A2, and A2 hybrid. In the present study, we found that the ability of M. catarrhalis to bind C3 correlated with UspA expression and that C3 binding contributed to serum resistance in a large number of clinical isolates. Recombinantly expressed UspA1 and A2 inhibit both the alternative and classical pathways, C3b deposition, and C3a generation when bound to the C3 molecule. We also revealed that the M. catarrhalis UspA-binding domain on C3b was located to C3d and that the major bacterial C3d-binding domains were within UspA1(299-452) and UspA2(165-318). The interaction with C3 was not species specific since UspA-expressing M. catarrhalis also bound mouse C3 that resulted in inhibition of the alternative pathway of mouse complement. Taken together, the binding of C3 to UspAs is an efficient strategy of Moraxella to block the activation of complement and to inhibit C3a-mediated inflammation.},
  author       = {Hallström, Teresia and Nordström, Therése and Tan, Thuan Tong and Manolov, Taras and Lambris, John D and Isenman, David E and Zipfel, Peter F and Blom, Anna and Riesbeck, Kristian},
  issn         = {1550-6606},
  language     = {eng},
  pages        = {3120--3129},
  publisher    = {ARRAY(0xb368fb0)},
  series       = {Journal of immunology (Baltimore, Md. : 1950)},
  title        = {Immune Evasion of Moraxella catarrhalis Involves Ubiquitous Surface Protein A-Dependent C3d Binding.},
  url          = {http://dx.doi.org/10.4049/jimmunol.1002621},
  volume       = {186},
  year         = {2011},
}