Abstract
Innate immunity is the first line of host defense against invading pathogens, and it is recognized by a variety of pattern recognition molecules, including mannose-binding lectin (MBL). MBL binds to mannose and N-acetylglucosamine residues present on the glycopolymers of microorganisms. Human serum MBL functions as an opsonin and activates the lectin complement pathway. However, which glycopolymer of microorganism is recognized by MBL is still uncertain. Here, we show that wall teichoic acid of Staphylococcus aureus, a bacterial cell surface glycopolymer containing N-acetylglucosamine residue, is a functional ligand of MBL. Whereas serum MBL in adults did not bind to wall teichoic acid because of an inhibitory effect of anti-wall teichoic acid antibodies, MBL in infants who had not yet fully developed their adaptive immunity could bind to S. aureus wall teichoic acid and then induced complement C4 deposition. Our data explain the molecular reasons of why MBL-deficient infants are susceptible to S. aureus infection.
Highlights
(GlcNAc) residues present on the glycopolymers of microorganisms [3]
Human mannose-binding lectin (MBL) Binding to S. aureus Cells Requires the S. aureus tagO Gene—We have previously reported that human MBL binds to S. aureus PG and activates the PG-dependent lectin complement pathway [21]
The wall teichoic acid (WTA)-deficient S. aureus ⌬tagO mutant was impaired in its binding capacity to MBL, and introduction of a plasmid-encoded tagO gene restored the binding ability, enabling us to demonstrate the evidence of direct binding between the MBL/MASP complex and purified S. aureus WTA
Summary
Linked to PG at the C6 position of N-acetylmuramic acid (MurNAc) (Ref. 18 and supplemental Fig. S1). Several reports have demonstrated that MBL bound to S. aureus induces activation of the complement pathway [15, 16, 21], which S. aureus glycopolymer is recognized by MBL is still uncertain. We have reported that human MBL binds to S. aureus PG and activates the lectin pathway [21] and two other studies have demonstrated MBL binding to S. aureus LTA [22, 23]. Infants who have low levels of both MBL and anti-WTA-antibodies have weak ability to activate the complement system. These results indicate that S. aureus WTA is an important pathogenassociated molecular pattern for the complement activation
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