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Ionic binding of C3 to the human pathogen Moraxella catarrhalis is a unique mechanism for combating innate immunity

Nordström, Therése LU ; Blom, Anna LU ; Tan, Thuan Tong LU ; Forsgren, Arne LU and Riesbeck, Kristian LU (2005) In Journal of Immunology 175(6). p.3628-3636
Abstract
Moraxella catarrhalis ubiquitous surface proteins A1 and A2 (UspA1/A2) interfere with the classical pathway of the complement system by binding C4b-binding protein. In this study we demonstrate that M. catarrhalis UspA1 and A2 noncovalently and in a dose-dependent manner bind both the third component of complement (C3) from EDTA-treated serum and methylamine-treated C3. In contrast, related Moraxella subspecies (n = 13) or other human pathogenic bacteria (n = 13) do not bind C3 or methylamine-treated C3. Experiments with recombinant proteins and M. catarrhalis mutants devoid of UspA1/A2 revealed that UspA1/A2 exert their actions by absorbing and neutralizing C3 from serum and restrain complement activation. UspA2 was responsible for most... (More)
Moraxella catarrhalis ubiquitous surface proteins A1 and A2 (UspA1/A2) interfere with the classical pathway of the complement system by binding C4b-binding protein. In this study we demonstrate that M. catarrhalis UspA1 and A2 noncovalently and in a dose-dependent manner bind both the third component of complement (C3) from EDTA-treated serum and methylamine-treated C3. In contrast, related Moraxella subspecies (n = 13) or other human pathogenic bacteria (n = 13) do not bind C3 or methylamine-treated C3. Experiments with recombinant proteins and M. catarrhalis mutants devoid of UspA1/A2 revealed that UspA1/A2 exert their actions by absorbing and neutralizing C3 from serum and restrain complement activation. UspA2 was responsible for most of the effect, and the Moraxella mutant lacking UspA2 was more sensitive to the lytic effect of human serum compared with the wild type. Interestingly, among the large number of bacteria analyzed, only M. catarrhalis has this unique ability to interfere with the innate immune system of complement by binding C3. (Less)
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author
organization
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type
Contribution to journal
publication status
published
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in
Journal of Immunology
volume
175
issue
6
pages
3628 - 3636
publisher
American Association of Immunologists
external identifiers
  • pmid:16148107
  • wos:000232010800025
  • scopus:24744450551
ISSN
1550-6606
language
English
LU publication?
yes
id
aa19f449-f3f7-4f37-ba29-b547af7cd3ae (old id 223710)
alternative location
http://www.jimmunol.org/cgi/content/full/175/6/3628
date added to LUP
2007-08-15 13:42:36
date last changed
2017-11-05 04:35:00
@article{aa19f449-f3f7-4f37-ba29-b547af7cd3ae,
  abstract     = {Moraxella catarrhalis ubiquitous surface proteins A1 and A2 (UspA1/A2) interfere with the classical pathway of the complement system by binding C4b-binding protein. In this study we demonstrate that M. catarrhalis UspA1 and A2 noncovalently and in a dose-dependent manner bind both the third component of complement (C3) from EDTA-treated serum and methylamine-treated C3. In contrast, related Moraxella subspecies (n = 13) or other human pathogenic bacteria (n = 13) do not bind C3 or methylamine-treated C3. Experiments with recombinant proteins and M. catarrhalis mutants devoid of UspA1/A2 revealed that UspA1/A2 exert their actions by absorbing and neutralizing C3 from serum and restrain complement activation. UspA2 was responsible for most of the effect, and the Moraxella mutant lacking UspA2 was more sensitive to the lytic effect of human serum compared with the wild type. Interestingly, among the large number of bacteria analyzed, only M. catarrhalis has this unique ability to interfere with the innate immune system of complement by binding C3.},
  author       = {Nordström, Therése and Blom, Anna and Tan, Thuan Tong and Forsgren, Arne and Riesbeck, Kristian},
  issn         = {1550-6606},
  language     = {eng},
  number       = {6},
  pages        = {3628--3636},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Ionic binding of C3 to the human pathogen Moraxella catarrhalis is a unique mechanism for combating innate immunity},
  volume       = {175},
  year         = {2005},
}