Whereas experimental murine periodontitis investigations have shown that periopathogenic bacteria induced alveolar bone destruction is mediated in part by costimulation of TLR2, TLR4, and TLR9 (56–58), outcomes from the current report imply that the commensal oral microbiota–driven alveolar bone loss is governed by TLR2, TLR4, and TLR9 signaling crosstalk. The gene discussed is TLR4; the disease is periodontitis.