Porphyromonas gingivalis sphingolipids impair neutrophil function and promote bacterial survival

Background: Porphyromonas gingivalis (P. gingivalis) is one of the few bacteria that can produce sphingolipids (SLs). Bacterial SLs have been shown to modulate the host immune response. Objective: Since neutrophil activation is critical for the pathogenesis of periodontal disease, we hypothesized that SL synthesis by P. gingivalis is important for neutrophil function. Design: We treated primary human neutrophils with P. gingivalis strains W83 that either produce SL (W83) or lack expression (W83 ΔSPT). We compared the phagocytosis capacity and toll-like receptor 2 (TLR2), TLR4, the adhesion molecule CD62L, and sphingosine 1 phosphate receptor 1 (S1PR1) expressions of the neutrophils. We evaluated the migration speed of neutrophils using microfluidic and transwell systems. We quantified their superoxide formation, measured neutrophil extracellular trap (NET), and inflammatory mediator release. Results: When P. gingivalis cannot synthesize SLs, this promotes early neutrophil recruitment, higher levels of phagocytosis, and a decrease in bacterial survival. P. gingivalis can stimulate TLR2 expression, prevent S1PR1 expression, and suppress the production of inflammatory mediators in the presence of SL expression. Conclusions: Our data suggest that SL synthesis is an efficient immune evasion mechanism of P. gingivalis, which dampens the inflammatory response of neutrophils to this endogenous pathogen.