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Haemophilus influenzae Type f Hijacks Vitronectin Using Protein H To Resist Host Innate Immunity and Adhere to Pulmonary Epithelial Cells.

Tamim, Al-Jubair LU ; Mukherjee, Oindrilla LU ; Oosterhuis, Sharon LU ; Singh, Birendra LU ; Su, Yu-Ching LU ; Fleury, Christophe LU ; Blom, Anna LU orcid ; Törnroth-Horsefield, Susanna LU and Riesbeck, Kristian LU orcid (2015) In Journal of Immunology 195(12). p.5688-5695
Abstract
The incidence of invasive Haemophilus influenzae type b (Hib) disease has significantly decreased since the introduction of an efficient vaccine against Hib. However, in contrast to Hib, infections caused by H. influenzae serotype f (Hif) are emerging. We recently did a whole genome sequencing of an invasive Hif isolate, and reported that Hif interacts with factor H by expressing protein H (PH). In this study, upon screening with various human complement regulators, we revealed that PH is also a receptor for vitronectin (Vn), an abundant plasma protein that regulates the terminal pathway of the human complement system in addition to being a component of the extracellular matrix. Bacterial Vn binding was significantly reduced when the lph... (More)
The incidence of invasive Haemophilus influenzae type b (Hib) disease has significantly decreased since the introduction of an efficient vaccine against Hib. However, in contrast to Hib, infections caused by H. influenzae serotype f (Hif) are emerging. We recently did a whole genome sequencing of an invasive Hif isolate, and reported that Hif interacts with factor H by expressing protein H (PH). In this study, upon screening with various human complement regulators, we revealed that PH is also a receptor for vitronectin (Vn), an abundant plasma protein that regulates the terminal pathway of the human complement system in addition to being a component of the extracellular matrix. Bacterial Vn binding was significantly reduced when the lph gene encoding PH was deleted in an invasive Hif isolate. The dissociation constant (KD) of the interaction between recombinant PH and Vn was 2.2 μM, as revealed by Biolayer interferometry. We found that PH has different regions for simultaneous interaction with both Vn and factor H, and that it recognized the C-terminal part of Vn (aa 352-362). Importantly, PH-dependent Vn binding resulted in better survival of the wild-type Hif or PH-expressing Escherichia coli when exposed to human serum. Finally, we observed that PH mediated an increased bacterial adherence to alveolar epithelial cells in the presence of Vn. In conclusion, our study reveals that PH most likely plays an important role in Hif pathogenesis by increasing serum resistance and adhesion to the airways. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
195
issue
12
pages
5688 - 5695
publisher
American Association of Immunologists
external identifiers
  • pmid:26538390
  • wos:000366735100019
  • scopus:84958280867
  • pmid:26538390
ISSN
1550-6606
DOI
10.4049/jimmunol.1501197
language
English
LU publication?
yes
id
87b8f0df-4293-428d-ad2d-e98addffa71f (old id 8243066)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26538390?dopt=Abstract
date added to LUP
2016-04-01 09:54:31
date last changed
2022-02-02 04:00:28
@article{87b8f0df-4293-428d-ad2d-e98addffa71f,
  abstract     = {{The incidence of invasive Haemophilus influenzae type b (Hib) disease has significantly decreased since the introduction of an efficient vaccine against Hib. However, in contrast to Hib, infections caused by H. influenzae serotype f (Hif) are emerging. We recently did a whole genome sequencing of an invasive Hif isolate, and reported that Hif interacts with factor H by expressing protein H (PH). In this study, upon screening with various human complement regulators, we revealed that PH is also a receptor for vitronectin (Vn), an abundant plasma protein that regulates the terminal pathway of the human complement system in addition to being a component of the extracellular matrix. Bacterial Vn binding was significantly reduced when the lph gene encoding PH was deleted in an invasive Hif isolate. The dissociation constant (KD) of the interaction between recombinant PH and Vn was 2.2 μM, as revealed by Biolayer interferometry. We found that PH has different regions for simultaneous interaction with both Vn and factor H, and that it recognized the C-terminal part of Vn (aa 352-362). Importantly, PH-dependent Vn binding resulted in better survival of the wild-type Hif or PH-expressing Escherichia coli when exposed to human serum. Finally, we observed that PH mediated an increased bacterial adherence to alveolar epithelial cells in the presence of Vn. In conclusion, our study reveals that PH most likely plays an important role in Hif pathogenesis by increasing serum resistance and adhesion to the airways.}},
  author       = {{Tamim, Al-Jubair and Mukherjee, Oindrilla and Oosterhuis, Sharon and Singh, Birendra and Su, Yu-Ching and Fleury, Christophe and Blom, Anna and Törnroth-Horsefield, Susanna and Riesbeck, Kristian}},
  issn         = {{1550-6606}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{5688--5695}},
  publisher    = {{American Association of Immunologists}},
  series       = {{Journal of Immunology}},
  title        = {{Haemophilus influenzae Type f Hijacks Vitronectin Using Protein H To Resist Host Innate Immunity and Adhere to Pulmonary Epithelial Cells.}},
  url          = {{http://dx.doi.org/10.4049/jimmunol.1501197}},
  doi          = {{10.4049/jimmunol.1501197}},
  volume       = {{195}},
  year         = {{2015}},
}