Bactericidal/Permeability-Increasing Protein Is an Enhancer of Bacterial Lipoprotein Recognition

Abstract

Adequate perception of immunologically important pathogen-associated molecular patterns like lipopolysaccharide and bacterial lipoproteins is essential for efficient innate and adaptive immune responses. In the context of Gram-negative infection, bactericidal/permeability-increasing protein (BPI) neutralizes endotoxic activity of lipopolysaccharides, and thus prohibits hyperactivation. So far, no immunological function of BPI has been described in Gram-positive infections. Here, we show a significant elevation of BPI in Gram-positive meningitis and, surprisingly, a positive correlation between BPI and pro-inflammatory markers like TNFα. To clarify the underlying mechanisms, we identify BPI ligands of Gram-positive origin, specifically bacterial lipopeptides and lipoteichoic acids, and determine essential structural motifs for this interaction. Importantly, the interaction of BPI with these newly defined ligands significantly enhances the immune response in peripheral blood mononuclear cells (PBMCs) mediated by Gram-positive bacteria, and thereby ensures their sensitive perception. In conclusion, we define BPI as an immune enhancing pattern recognition molecule in Gram-positive infections.

A Human IgSF Cell-Surface Interactome Reveals a Complex Network of Protein-Protein Interactions

“…We observed SLAMF9 binding to bactericidal permeability-increasing protein (BPI) and IGSF10 ( Figure 2 C). BPI is a neutrophil-derived antibiotic protein that participates in bacteria killing through its highly cationic N-terminal region ( Bülow et al., 2018 ). The C-terminal region of BPI exhibits no bactericidal activity and is believed to interact with other proteins and function in different processes.…”

Identification of key candidate biomarkers for severe influenza infection by integrated bioinformatical analysis and initial clinical validation

“…It also reflected disease status or predicted influenza patients' outcome. Among them, some proteins related to specific neutrophils granules, such as bactericidal/permeability‐increasing (BPI) protein and matrix metalloproteinase‐8 (MMP8) protein, were generally more abundant in relative severe influenza cases 41,42 . Specially, it has been reported recently that originally identified as neutrophil collagenase, MMP8 was elevated after influenza infection 43 .…”

Low-Avidity Autoantibodies against Bactericidal/Permeability-Increasing Protein Occur in Gram-Negative and Gram-Positive Bacteremia

“…Our findings suggest that this pathway predominates in acute bacteremia. There has been a report of BPI binding to both LPS and lipopeptides on S. aureus , enhancing bacterial lipoprotein recognition ( 41 ). The bacteremia presumably facilitates delivery of BPI complexed with GNB/GPB to the marginal zone of the spleen, resulting in activation of their polyreactive B-cell receptor (BCR) and Toll-like receptor (TLR) to result in low-avidity IgG autoantibodies.…”