Recognition of pneumococcal peptidoglycan: an expanded, pivotal role for LPS binding protein.
Lipopolysaccharide binding protein (LBP) has a well-established role in LPS-induced immune responses. Here, we report that LBP also plays an essential role in the innate immune response to Gram-positive pneumococci, specifically to their major inflammatory component, pneumococcal cell wall (PCW). LBP was present in the CSF of patients with meningitis, and LBP-deficient mice failed to develop meningeal inflammation. LBP enhanced PCW-induced cell signaling and TNF-alpha release. LBP bound specifically to PCW multimers, indicating novel lipid-independent binding capability for LBP. We propose the iterative anionic groups along the glycan backbone of the cell wall are a crucial structure for recognition by LBP. Such a function for LBP expands its role to Gram-positive infections.
Weber
Joerg R
JR
Department of Neurology, Universitaetsklinikum Charité, Humboldt University, 10117 Berlin, Germany. joerg.weber@charite.de
Freyer
Dorette
D
Alexander
Christian
C
Schröder
Nicolas W J
NW
Reiss
Anja
A
Küster
Carsten
C
Pfeil
Dagmar
D
Tuomanen
Elaine I
EI
Schumann
Ralf R
RR
D000209:Acute-Phase Proteins; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D016022:Case-Control Studies; D002473:Cell Wall / Q000737:chemistry / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D009569:Nitric Oxide / Q000096:biosynthesis; D010457:Peptidoglycan / Q000276:immunology*; D010713:Phosphatidylcholines / Q000276:immunology; D011008:Pneumococcal Infections / Q000209:etiology; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity; D051193:Toll-Like Receptors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D009569:Nitric Oxide; D010457:Peptidoglycan; D010713:Phosphatidylcholines; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein