Abstract
Porphyromonas gingivalis is a key bacterium in chronic periodontitis, which is associated with several chronic inflammatory diseases. Lipopolysaccharides from P. gingivalis (Pg LPS) can activate multiple cell types via the production of pro-inflammatory cytokines. The receptors for Pg LPS have initially been reported as TLR2, contrasting with the well-studied TLR4 receptor for E. coli LPS; this observation remains controversial since synthetic Pg lipid A activates TLR4 but not TLR2. Despite this observation, the dogma of Pg LPS-mediated TLR2 activation remains the basis of many hypotheses and result interpretations. In the present work, we aimed at determining whether TLR4 or TLR2, or both, mediate Pg LPS pro-inflammatory activity using Pg LPS with different grades of purity, instead of synthetic lipid A from Pg LPS. Here we show that Pg LPS 1) acts exclusively through TLR4, and 2) are differently recognized by mouse and human TLR4 both in vitro and in vivo. Taken together, our results suggest that Pg LPS activity is mediated exclusively through TLR4 and only weakly induces proinflammatory cytokine secretion in mouse models. Caution should be taken when extrapolating data from mouse systems exposed to Pg or Pg LPS to humans.
Highlights
The innate immune system is responsible for an inflammatory response necessary for the recruitment and activation of the adaptive immune system
In C3H/HeJ mice, which are deficient for TLR4, Pg LPS exhibits an activity suggesting that its effect is mediated by TLR218,19
We tested the hypothesis that lipoprotein contamination in standard Pg LPS (STD Pg LPS) preparations may be responsible for TLR2 activation by using both standard and ultrapure Pg LPS (UP pg LPS)
Summary
The innate immune system is responsible for an inflammatory response necessary for the recruitment and activation of the adaptive immune system. LPS from Escherichia coli (Ec LPS), a gram-negative bacteria, targets TLR4 and activates the NF-κB signaling pathway, leading to the secretion of inflammatory cytokines, such as Tumor Necrosis Factor α (TNF-α) and Interleukin 6 (IL-6), and chemokines, such as Monocyte Chemoattractant Protein 1 (MCP-1)[7]. Another gram-negative bacterium, Porphyromonas gingivalis is a well-known bacteria responsible for the development of chronic periodontitis[8]. We aimed at determining whether TLR4 and/or TLR2 are responsible for Pg LPS pro-inflammatory activity
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