with a resilience between a mouse and human
Porphyromonas gingivalis is a key bacterium in chronic periodontitis, which is associated with several chronic inlammatory diseases. Lipopolysaccharides from P. gingivalis (Pg LPS) can activate multiple cell types via the production of pro-inlammatory 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-inlammatory activity using Pg LPS with diferent 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 diferently 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 proinlammatory cytokine secretion in mouse models. Caution should be taken when extrapolating data from mouse systems exposed to Pg or Pg LPS to humans.