L-Ficolin and Capsular Polysaccharide-Specific IgG in Cord Serum Contribute Synergistically to Opsonophagocytic Killing of Serotype III and V Group B Streptococci

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>Group B streptococci (GBS;<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Streptococcus agalactiae</jats:named-content>) are the most common cause of neonatal sepsis and meningitis. Serotype-specific IgG antibody is known to protect neonates against GBS infections by promoting opsonophagocytosis. The L-ficolin-mediated lectin pathway of the complement is also a potential mechanism for opsonization of GBS, because L-ficolin activates the complement after binding to serotype Ib, III, V, VI, and VIII GBS. In the present study, we investigated how L-ficolin and serotype-specific IgG in cord sera contribute to opsonophagocytic killing of GBS. Neither L-ficolin nor serotype-specific IgG concentrations correlated with C3b deposition on serotype Ib and VI GBS, suggesting L-ficolin- and serotype-specific IgG-independent mechanisms of complement activation. The percentage of serotype VIII GBS killed was high regardless of the concentration of L-ficolin and IgG. In contrast, L-ficolin and serotype-specific IgG can each initiate C3b deposition on serotype III and V GBS and promote phagocytosis by polymorphonuclear leukocytes, but L-ficolin and serotype-specific IgG together promote opsonophagocytic killing to a greater extent than does either alone<jats:italic>in vitro</jats:italic>. This synergy was observed when serotype III-specific IgG concentrations were between 1 and 6 μg/ml and when serotype V-specific IgG concentrations were between 2 and 5 μg/ml. Concentrations of serotype III-specific IgG in cord blood above 7 μg/ml are considered protective for neonates colonized with GBS, but most neonates with IgG levels of less than 7 μg/ml do not develop GBS infections. The data presented here suggest that L-ficolin enhances opsonophagocytosis of serotype III and V GBS when serotype-specific IgG alone is suboptimal for protection.</jats:p>

The Group B Streptococcus–Secreted Protein CIP Interacts with C4, Preventing C3b Deposition via the Lectin and Classical Complement Pathways

“…Recent studies highlighted a role of the LP L-ficolin/ MASP complexes in the formation of the C4bC2a convertase on the GBS surface, initiation of C3b deposition, and phagocytic killing in the absence of specific Abs (36), a process that can be further amplified by anti-capule polysaccaride IgG and the AP convertase. The same authors suggested that deficiencies in L-ficolin in cord serum could be a risk factor for neonatal GBS infection (37). We concluded that, in absence of specific Abs, CIP could interfere with LP complement amplification.…”

Role of Ficolin-A and Lectin Complement Pathway in the Innate Defense against Pathogenic Aspergillus Species

“…There are now a number of studies that have confirmed that ficolin-A or its human homologue L-ficolin forms an integral part of the innate immune response to several bacteria and viruses (14)(15)(16)(17). Previous research has highlighted that L-ficolin opsonization of the bacterial species Salmonella enterica serovar Typhimurium (S. Typhimurium) and Streptococcus agalactiae (S. agalactiae) led to better phagocytosis and lectin complement pathway activation (14,15).…”

“…Previous research has highlighted that L-ficolin is able to function as an opsonin and enhance phagocytosis of S. Typhimurium and S. agalactiae (14,15). Due to the small size of the conidia, they can penetrate deep into the lungs, where they initially encounter the lung epithelium, in particular, type II pneumocytes (35).…”

“…Previous research has highlighted that L-ficolin opsonization of the bacterial species Salmonella enterica serovar Typhimurium (S. Typhimurium) and Streptococcus agalactiae (S. agalactiae) led to better phagocytosis and lectin complement pathway activation (14,15). While ficolins have also been shown to interact with viruses such as influenza virus and hepatitis C virus by inhibiting their replication or leading to complement activation, the role of ficolins in the defense against medically important fungal pathogens has not been greatly investigated to date (16,17).…”

Blood Collection Tubes Influence Serum Ficolin-1 and Ficolin-2 Levels

“…Ficolin-2 is known to bind many acetylated ligands (5) and various biological ligands, such as apoptotic cells (6), and may be important in renal transplantation (7) and preeclampsia (8). It also binds to several significant human pathogens, like group B streptococcus (9) and Salmonella enterica serovar Typhimurium (10), and to many Gram-positive bacterial teichoic acids (11). Thus, it may be important in host defense against these pathogens as well.…”