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Naturally Occurring IgG Antibodies Provide Innate Protection against Vibrio cholerae Bacteremia by Recognition of the Outer Membrane Protein U

Aung, Kyaw Min; Sjöström, Annika E.; von Pawel-Rammingen, Ulrich; Riesbeck, Kristian LU ; Uhlin, Bernt Eric and Wai, Sun Nyunt (2016) In Journal of Innate Immunity 8(3). p.269-283
Abstract

Cholera epidemics are caused by Vibrio cholerae serogroups O1 and O139, whereas strains collectively known as non-O1/non-O139 V. cholerae are found in cases of extraintestinal infections and bacteremia. The mechanisms and factors influencing the occurrence of bacteremia and survival of V. cholerae in normal human serum have remained unclear. We found that naturally occurring IgG recognizing V. cholerae outer membrane protein U (OmpU) mediates a serum-killing effect in a complement C1q-dependent manner. Moreover, outer membrane vesicles (OMVs) containing OmpU caused enhanced survival of highly serum-sensitive classical V. cholerae in a dose-dependent manner. OMVs from wild-type and ompU mutant V. cholerae thereby provided a novel means... (More)

Cholera epidemics are caused by Vibrio cholerae serogroups O1 and O139, whereas strains collectively known as non-O1/non-O139 V. cholerae are found in cases of extraintestinal infections and bacteremia. The mechanisms and factors influencing the occurrence of bacteremia and survival of V. cholerae in normal human serum have remained unclear. We found that naturally occurring IgG recognizing V. cholerae outer membrane protein U (OmpU) mediates a serum-killing effect in a complement C1q-dependent manner. Moreover, outer membrane vesicles (OMVs) containing OmpU caused enhanced survival of highly serum-sensitive classical V. cholerae in a dose-dependent manner. OMVs from wild-type and ompU mutant V. cholerae thereby provided a novel means to verify by extracellular transcomplementation the involvement of OmpU. Our data conclusively indicate that loss, or reduced expression, of OmpU imparts resistance to V. cholerae towards serum killing. We propose that the difference in OmpU protein levels is a plausible reason for differences in serum resistance and the ability to cause bacteremia observed among V. cholerae biotypes. Our findings provide a new perspective on how naturally occurring antibodies, perhaps induced by members of the microbiome, may play a role in the recognition of pathogens and the provocation of innate immune defense against bacteremia.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
<italic>Vibrio cholerae</italic>, C1q#, Naturally occurring IgG antibodies, Outer membrane protein U, Outer membrane vesicles, Serum resistance
in
Journal of Innate Immunity
volume
8
issue
3
pages
269 - 283
publisher
Karger
external identifiers
  • scopus:84961223388
  • wos:000375803900006
ISSN
1662-811X
DOI
10.1159/000443646
language
English
LU publication?
yes
id
5e18c9e0-c20e-47ce-9ab9-908d02a09e2d
date added to LUP
2016-07-08 11:05:24
date last changed
2017-01-01 08:30:08
@article{5e18c9e0-c20e-47ce-9ab9-908d02a09e2d,
  abstract     = {<p>Cholera epidemics are caused by Vibrio cholerae serogroups O1 and O139, whereas strains collectively known as non-O1/non-O139 V. cholerae are found in cases of extraintestinal infections and bacteremia. The mechanisms and factors influencing the occurrence of bacteremia and survival of V. cholerae in normal human serum have remained unclear. We found that naturally occurring IgG recognizing V. cholerae outer membrane protein U (OmpU) mediates a serum-killing effect in a complement C1q-dependent manner. Moreover, outer membrane vesicles (OMVs) containing OmpU caused enhanced survival of highly serum-sensitive classical V. cholerae in a dose-dependent manner. OMVs from wild-type and ompU mutant V. cholerae thereby provided a novel means to verify by extracellular transcomplementation the involvement of OmpU. Our data conclusively indicate that loss, or reduced expression, of OmpU imparts resistance to V. cholerae towards serum killing. We propose that the difference in OmpU protein levels is a plausible reason for differences in serum resistance and the ability to cause bacteremia observed among V. cholerae biotypes. Our findings provide a new perspective on how naturally occurring antibodies, perhaps induced by members of the microbiome, may play a role in the recognition of pathogens and the provocation of innate immune defense against bacteremia.</p>},
  author       = {Aung, Kyaw Min and Sjöström, Annika E. and von Pawel-Rammingen, Ulrich and Riesbeck, Kristian and Uhlin, Bernt Eric and Wai, Sun Nyunt},
  issn         = {1662-811X},
  keyword      = {<italic>Vibrio cholerae</italic>,C1q#,Naturally occurring IgG antibodies,Outer membrane protein U,Outer membrane vesicles,Serum resistance},
  language     = {eng},
  number       = {3},
  pages        = {269--283},
  publisher    = {Karger},
  series       = {Journal of Innate Immunity},
  title        = {Naturally Occurring IgG Antibodies Provide Innate Protection against Vibrio cholerae Bacteremia by Recognition of the Outer Membrane Protein U},
  url          = {http://dx.doi.org/10.1159/000443646},
  volume       = {8},
  year         = {2016},
}