Back to Search
Start Over
A human secretome library screen reveals a role for Peptidoglycan Recognition Protein 1 in Lyme borreliosis.
- Source :
- PLoS Pathogens, Vol 16, Iss 11, p e1009030 (2020)
- Publication Year :
- 2020
- Publisher :
- Public Library of Science (PLoS), 2020.
-
Abstract
- Lyme disease, the most common vector-borne illness in North America, is caused by the spirochete Borrelia burgdorferi. Infection begins in the skin following a tick bite and can spread to the hearts, joints, nervous system, and other organs. Diverse host responses influence the level of B. burgdorferi infection in mice and humans. Using a systems biology approach, we examined potential molecular interactions between human extracellular and secreted proteins and B. burgdorferi. A yeast display library expressing 1031 human extracellular proteins was probed against 36 isolates of B. burgdorferi sensu lato. We found that human Peptidoglycan Recognition Protein 1 (PGLYRP1) interacted with the vast majority of B. burgdorferi isolates. In subsequent experiments, we demonstrated that recombinant PGLYRP1 interacts with purified B. burgdorferi peptidoglycan and exhibits borreliacidal activity, suggesting that vertebrate hosts may use PGLYRP1 to identify B. burgdorferi. We examined B. burgdorferi infection in mice lacking PGLYRP1 and observed an increased spirochete burden in the heart and joints, along with splenomegaly. Mice lacking PGLYRP1 also showed signs of immune dysregulation, including lower serum IgG levels and higher levels of IFNγ, CXCL9, and CXCL10.Taken together, our findings suggest that PGLYRP1 plays a role in the host's response to B. burgdorferi and further demonstrate the utility of expansive yeast display screening in capturing biologically relevant interactions between spirochetes and their hosts.
- Subjects :
- Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Subjects
Details
- Language :
- English
- ISSN :
- 15537366 and 15537374
- Volume :
- 16
- Issue :
- 11
- Database :
- Directory of Open Access Journals
- Journal :
- PLoS Pathogens
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.8aa2ff8b5a8c444497679cc5ca22c95e
- Document Type :
- article
- Full Text :
- https://doi.org/10.1371/journal.ppat.1009030