Pneumolysin binds to the mannose receptor C type 1 (MRC-1) leading to anti-inflammatory responses and enhanced pneumococcal survival.
Animals
Bacterial Load
Bacterial Proteins
/ genetics
Cell Line
Dendritic Cells
/ immunology
Forkhead Transcription Factors
/ biosynthesis
Humans
Interferon-gamma
/ biosynthesis
Interleukin-4
/ biosynthesis
Macrophages, Alveolar
/ immunology
Membrane Glycoproteins
Mice
Neutrophil Infiltration
/ immunology
Pneumococcal Infections
/ pathology
RNA Interference
RNA, Small Interfering
/ genetics
Receptors, Immunologic
/ genetics
Streptococcus pneumoniae
/ genetics
Streptolysins
/ genetics
Suppressor of Cytokine Signaling 1 Protein
/ biosynthesis
T-Lymphocytes
/ immunology
Virulence Factors
Journal
Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
07
02
2018
accepted:
01
10
2018
pubmed:
14
11
2018
medline:
18
6
2019
entrez:
14
11
2018
Statut:
ppublish
Résumé
Streptococcus pneumoniae (the pneumococcus) is a major cause of mortality and morbidity globally, and the leading cause of death in children under 5 years old. The pneumococcal cytolysin pneumolysin (PLY) is a major virulence determinant known to induce pore-dependent pro-inflammatory responses. These inflammatory responses are driven by PLY-host cell membrane cholesterol interactions, but binding to a host cell receptor has not been previously demonstrated. Here, we discovered a receptor for PLY, whereby pro-inflammatory cytokine responses and Toll-like receptor signalling are inhibited following PLY binding to the mannose receptor C type 1 (MRC-1) in human dendritic cells and mouse alveolar macrophages. The cytokine suppressor SOCS1 is also upregulated. Moreover, PLY-MRC-1 interactions mediate pneumococcal internalization into non-lysosomal compartments and polarize naive T cells into an interferon-γ
Identifiants
pubmed: 30420782
doi: 10.1038/s41564-018-0280-x
pii: 10.1038/s41564-018-0280-x
pmc: PMC6298590
mid: EMS79869
doi:
Substances chimiques
Bacterial Proteins
0
Forkhead Transcription Factors
0
Foxp3 protein, mouse
0
IFNG protein, mouse
0
MRC1 protein, human
0
Membrane Glycoproteins
0
RNA, Small Interfering
0
Receptors, Immunologic
0
Socs1 protein, mouse
0
Streptolysins
0
Suppressor of Cytokine Signaling 1 Protein
0
Virulence Factors
0
plY protein, Streptococcus pneumoniae
0
Interleukin-4
207137-56-2
Interferon-gamma
82115-62-6
Types de publication
Letter
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
62-70Subventions
Organisme : Wellcome Trust
ID : 204457/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P011284/1
Pays : United Kingdom
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