Neisseria gonorrhoeae co-opts C4b-binding protein to enhance complement-independent survival from neutrophils

Abstract

Neisseria gonorrhoeae (Gc) is a human-specific pathogen that causes the sexually transmitted infection gonorrhea. Gc survives in neutrophil-rich gonorrheal secretions, and recovered bacteria predominantly express phase-variable, surface-expressed opacity-associated (Opa) proteins (Opa+). However, expression of Opa proteins like OpaD decreases Gc survival when exposed to human neutrophils ex vivo. Here, we made the unexpected observation that incubation with normal human serum, which is found in inflamed mucosal secretions, enhances survival of Opa+ Gc from primary human neutrophils. We directly linked this phenomenon to a novel complement-independent function for C4b-binding protein (C4BP). When bound to the bacteria, C4BP was necessary and sufficient to suppress Gc-induced neutrophil reactive oxygen species production and prevent neutrophil phagocytosis of Opa+ Gc. This research identifies for the first time a complement-independent role for C4BP in enhancing the survival of a pathogenic bacterium from phagocytes, thereby revealing how Gc exploits inflammatory conditions to persist at human mucosal surfaces.

Proteomics Clustering Research of ITRAQ Markers in Plasma of AIDS Patients with Different Chinese Medicine Syndromes

“…Secretion of other pro-inflammatory cytokines also increases CRP concentrations, exacerbating the inflammatory process ( 22 ). C4BP is a glycoprotein in human serum and inhibits complement activity in classical and mannose-binding lectin pathways, preventing excessive inflammation and tissue damage ( 23 ).Pathogens can absorb C4BP on the cell surface to escape complement attack ( 24 ).The altered expression level of C4BP protein reflects the neuroinflammatory state of the host and can be used as a potential biomarker of MDD ( 25 ).…”

Neisseria gonorrhoeaescavenges host sialic acid for Siglec-mediated, complement-independent suppression of neutrophil activation

“…Infection of primary human neutrophils with TIV+ Gc and evaluation by imaging flow cytometry was performed as described (42, 68, 92). Because sialylation reduced bacterial binding of the goat anti-Gc antibody (Biosource) to almost undetectable levels (data not shown), extracellular Gc were recognized instead with H.5 anti-PorB, followed by AF647-coupled goat anti-mouse antibody.…”

Neisseria gonorrhoeae scavenges host sialic acid for Siglec-mediated, complement-independent suppression of neutrophil activation

“…Infection of primary human neutrophils with TIV+ Gc and evaluation by imaging flow cytometry was performed as described ( 42 , 68 , 92 ). Because sialylation reduced bacterial binding of the goat anti-Gc antibody (Biosource) to almost undetectable levels (data not shown), extracellular Gc was recognized instead with H.5 anti-PorB, followed by AF647-coupled goat anti-mouse antibody.…”