CCN1 is an opsonin for bacterial clearance and a direct activator of Toll-like receptor signaling.

Nature Communications
Joon-Il Jun, Lester F Lau

Abstract

Expression of the matricellular protein CCN1 (CYR61) is associated with inflammation and is required for successful wound repair. Here, we show that CCN1 binds bacterial pathogen-associated molecular patterns including peptidoglycans of Gram-positive bacteria and lipopolysaccharides of Gram-negative bacteria. CCN1 opsonizes methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa and accelerates their removal by phagocytosis and increased production of bactericidal reactive oxygen species in macrophages through the engagement of integrin αvβ3. Mice with myeloid-specific Ccn1 deletion and knock-in mice expressing CCN1 unable to bind αvβ3 are more susceptible to infection by S. aureus or P. aeruginosa, resulting in increased mortality and organ colonization. Furthermore, CCN1 binds directly to TLR2 and TLR4 to activate MyD88-dependent signaling, cytokine expression and neutrophil mobilization. CCN1 is therefore a pattern recognition receptor that opsonizes bacteria for clearance and functions as a damage-associated molecular pattern to activate inflammatory responses, activities that contribute to wound healing and tissue repair.

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Citations

Oct 7, 2020·Trends in Biochemical Sciences·Martijn A NolteCoert Margadant
Oct 28, 2020·International Journal of Molecular Sciences·Yin ZhuDuo Zhang
Aug 5, 2021·Signal Transduction and Targeted Therapy·Danyang Li, Minghua Wu

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Datasets Mentioned

BETA
HY-18950

Methods Mentioned

BETA
flow cytometry
chip
surface
fluorescence microscopy
lavage
ELISA
blood drawn
GTPase
nucleotide exchange
PCR

Software Mentioned

Biacore T - 200
Photoshop
CytoExpert
Image J

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