Human Serum Mannose-binding Lectin Senses Wall Teichoic Acid Glycopolymer of Staphylococcus aureus, Which Is Restricted in Infancy

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 antiwall 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.

Specific Serum Ig Recognizing Staphylococcal Wall Teichoic Acid Induces Complement-Mediated Opsonophagocytosis against Staphylococcus aureus

“…Based on these observations, we proposed that WTA-recognizing serum Abs might activate the anti-WTA-IgG-mediated complement pathway in the MBL(2) adult serum. We also proposed that MBL(2) adults who lack a lectin complement pathway produce specific serum Abs against S. aureus WTA to compensate for the deficiency of lectin complement pathway-mediated innate immunity (12). However, there is no direct evidence supporting these hypotheses.…”

“…Recently, we reported that the purified human MBL/MBLassociated serine proteases (MASP) complex specifically binds to wild-type S. aureus, but not to the WTA-deficient S. aureus DtagO mutant, indicating that MBL recognizes WTA in vitro (12). However, intriguingly, the serum MBL/MASP complex in adults does not bind to WTA because of an inhibitory effect of anti-WTA-IgG.…”

“…have not yet fully developed their adaptive immunity can bind to S. aureus WTA and then induce complement C4 deposition (12). Furthermore, we also demonstrated that the adult serum that does not contain serum MBL [MBL (2) serum] has the ability to deposit C4 on wild-type S. aureus, as does the adult serum that contains sufficient amounts of serum MBL [MBL(+) serum], but the same serum cannot induce C4 deposition on S. aureus DtagO mutant cells at a low serum concentration.…”

Adenosine derived from Staphylococcus aureus-engulfed macrophages functions as a potent stimulant for the induction of inflammatory cytokines in mast cells

“…Recently, we screened mutant strains of S. aureus that lack various cell wall components in order to determine which molecules of the cell wall are recognized by host innate immune receptors. Among them, we demonstrated that wall teichoic acid (WTA) of S. aureus is a native ligand of human mannose binding lectin (MBL), a typical recognition molecule involved in the activation of the human lectin complement pathway (14), and that triacylated lipoproteins but not LTA derived from S. aureus are major ligands of mammalian Toll-like receptor-2 (15). Here, we provide additional evidence that adenosine released from S. aureus-engulfed macrophages can function as an inducing molecule of inflammatory cytokines in mast cells.…”

Pathways and roles of wall teichoic acid glycosylation in Staphylococcus aureus

“…Remarkably, S. aureus WTA contributes to biofilm formation (Vergara-Irigaray et al, 2008), adhesion to epithelial (Weidenmaier et al, 2004) and endothelial cells, and is important for severe invasive infections such as endocarditis (Weidenmaier et al, 2005). S. aureus WTA elicits robust antibody responses in humans and activates the human complement system via both the classical and the mannose-binding lectin pathway leading to opsonophagocytosis (Jung et al, 2012;Kurokawa et al, 2013;Park et al, 2010). How variation of WTA structure may affect the interaction of S. aureus with the innate and adaptive immune systems remains to be investigated.…”