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PRELP enhances host innate immunity against the respiratory tract pathogen moraxella catarrhalis

Liu, Guanghui LU ; Ermert, David LU ; Johansson, Martin E. LU ; Singh, Birendra LU ; Su, Shanice YC LU ; Paulsson, Magnus LU ; Riesbeck, Kristian LU and Blom, Anna M. LU (2017) In Journal of Immunology 198(6). p.2330-2340
Abstract

Respiratory tract infections are one of the leading causes of mortality worldwide urging better understanding of interactions between pathogens causing these infections and the host. Here we report that an extracellular matrix component proline/arginine-rich end leucine-rich repeat protein (PRELP) is a novel antibacterial component of innate immunity.We detected the presence of PRELP in human bronchoalveolar lavage fluid and showed that PRELP can be found in alveolar fluid, resident macrophages/monocytes, myofibroblasts, and the adventitia of blood vessels in lung tissue. PRELP specifically binds respiratory tract pathogens Moraxella catarrhalis, Haemophilus influenzae, and Streptococcus pneumoniae, but not other bacterial pathogens... (More)

Respiratory tract infections are one of the leading causes of mortality worldwide urging better understanding of interactions between pathogens causing these infections and the host. Here we report that an extracellular matrix component proline/arginine-rich end leucine-rich repeat protein (PRELP) is a novel antibacterial component of innate immunity.We detected the presence of PRELP in human bronchoalveolar lavage fluid and showed that PRELP can be found in alveolar fluid, resident macrophages/monocytes, myofibroblasts, and the adventitia of blood vessels in lung tissue. PRELP specifically binds respiratory tract pathogens Moraxella catarrhalis, Haemophilus influenzae, and Streptococcus pneumoniae, but not other bacterial pathogens tested. We focused our study on M. catarrhalis and found that PRELP binds the majority of clinical isolates of M. catarrhalis (n = 49) through interaction with the ubiquitous surface protein A2/A2H. M. catarrhalis usually resists complement-mediated serum killing by recruiting to its surface a complement inhibitor C4b-binding protein, which is also a ligand for PRELP. We found that PRELP competitively inhibits binding of C4b-binding protein to bacteria, which enhances membrane attack complex formation on M. catarrhalis and thus leads to increased serum sensitivity. Furthermore, PRELP enhances phagocytic killing of serum-opsonized M. catarrhalis by human neutrophils in vitro. Moreover, PRELP reduces Moraxella adherence to and invasion of human lung epithelial A549 cells. Taken together, PRELP enhances host innate immunity against M. catarrhalis through increasing complement-mediated attack, improving phagocytic killing activity of neutrophils, and preventing bacterial adherence to lung epithelial cells.

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author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
198
issue
6
pages
11 pages
publisher
American Association of Immunologists
external identifiers
  • scopus:85014593282
  • wos:000395911700013
ISSN
0022-1767
DOI
10.4049/jimmunol.1601319
language
English
LU publication?
yes
id
323c862e-9a4b-4c11-b87f-54e43a733bd1
date added to LUP
2017-04-10 16:22:25
date last changed
2017-09-18 13:31:59
@article{323c862e-9a4b-4c11-b87f-54e43a733bd1,
  abstract     = {<p>Respiratory tract infections are one of the leading causes of mortality worldwide urging better understanding of interactions between pathogens causing these infections and the host. Here we report that an extracellular matrix component proline/arginine-rich end leucine-rich repeat protein (PRELP) is a novel antibacterial component of innate immunity.We detected the presence of PRELP in human bronchoalveolar lavage fluid and showed that PRELP can be found in alveolar fluid, resident macrophages/monocytes, myofibroblasts, and the adventitia of blood vessels in lung tissue. PRELP specifically binds respiratory tract pathogens Moraxella catarrhalis, Haemophilus influenzae, and Streptococcus pneumoniae, but not other bacterial pathogens tested. We focused our study on M. catarrhalis and found that PRELP binds the majority of clinical isolates of M. catarrhalis (n = 49) through interaction with the ubiquitous surface protein A2/A2H. M. catarrhalis usually resists complement-mediated serum killing by recruiting to its surface a complement inhibitor C4b-binding protein, which is also a ligand for PRELP. We found that PRELP competitively inhibits binding of C4b-binding protein to bacteria, which enhances membrane attack complex formation on M. catarrhalis and thus leads to increased serum sensitivity. Furthermore, PRELP enhances phagocytic killing of serum-opsonized M. catarrhalis by human neutrophils in vitro. Moreover, PRELP reduces Moraxella adherence to and invasion of human lung epithelial A549 cells. Taken together, PRELP enhances host innate immunity against M. catarrhalis through increasing complement-mediated attack, improving phagocytic killing activity of neutrophils, and preventing bacterial adherence to lung epithelial cells.</p>},
  author       = {Liu, Guanghui and Ermert, David and Johansson, Martin E. and Singh, Birendra and Su, Shanice YC and Paulsson, Magnus and Riesbeck, Kristian and Blom, Anna M.},
  issn         = {0022-1767},
  language     = {eng},
  month        = {03},
  number       = {6},
  pages        = {2330--2340},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {PRELP enhances host innate immunity against the respiratory tract pathogen moraxella catarrhalis},
  url          = {http://dx.doi.org/10.4049/jimmunol.1601319},
  volume       = {198},
  year         = {2017},
}