The membrane attack complex (MAC) generated after complement activation readily lyses the plasma membranes of most Gram-negative bacteria, but it poorly lyses those of Gram-positive bacteria because of their thick peptidoglycan layers (1). Thus, many reports have suggested that serum-antibody-mediated opsonophagocytotic bacterial killing is necessary to increase the bactericidal efficiency of the MAC against pathogenic Gram-positive bacterial infection (2). Wall teichoic acid (WTA) of Staphylococcus aureus is a major cell envelope-associated glycopolymer that is a key molecule in promoting colonization during S. aureus infection. We recently reported that S. aureus WTA functions as a ligand of human serum mannose-binding lectin (MBL), a recognition molecule of the lectin complement pathway (3). Intriguingly, serum MBL in adults does not bind to WTA because of an inhibitory effect of serum anti-WTA-immunoglobulin (IgG). Here, to examine the biological function of human anti-WTA-IgG, serum, anti-WTA-IgG was recently purified to homogeneity using a purified S. aureus WTA-coupled affinity column. The purified anti-WTA-IgG contained the IgG2 subclass as a major component and specifically induced C4 and C3 deposition on the S. aureus surface in the anti-WTA-IgG-depleted serum, but not in C1q-deficient serum. Furthermore, the anti-WTA-IgG-dependent C3 deposition induced phagocytosis of S. aureus cells by human polymorphonuclear leukocytes. These results demonstrate that serum anti-WTA-IgG is a real trigger for the induction of classical complement-dependent opsonophagocytosis against S. aureus. Our results also support the purified WTA of S. aureus can be used as putative vaccine candidate and the purified human anti-WTA-IgG can be useful for the plausible therapeutic antibodies against methicillin-resistanr S. aureus (MRSA). Furthermore, our results demonstrate that a lack of the lectin complement pathway in MBL-deficient adults is compensated by antigen-specific antibody-mediated adaptive immunity.
한국생물공학회 [The Korean Society for Biotechnology and Bioengineering]
설립연도
1984
분야
공학>생물공학
소개
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