gingivalis strains exhibited reduced periodontal bone loss, compared with infection with fimbriated strains (Jotwani & Cutler, 2004). Moreover, immunization against P. gingivalis fimbriae protected against bone loss in gnothobiotic rats (Malek et al., 1994; Sharma et al., 2001). Other properties of both major and minor fimbriae are the induction of proinflammatory cytokines and production of matrix metalloproteinases (MMPs), such as IL-1, IL-6, IL-8, TNF-α and MMP-9, by various host cells (Jotwani et al., 2010; Ogawa et al., 1994; Pollreisz et al., 2010; Takahashi et al., 2006). Porphyromonas gingivalis fimbriae can signal through either TLR2 or TLR4. Activation of TLR2 by fimbriae results in a differential

signalling JQ1 mouse pattern compared with activation by P. gingivalis LPS (Hajishengallis et al., 2006). Fimbriae can directly induce two distinct signalling pathways, one that mediates production of proinflammatory cytokines, such as IL-6 and TNF-α, and another that mediates the expression of cell adhesion molecules, such as ICAM-1 (Hajishengallis et al., 2009). On the other hand, signalling through TLR4 requires an additional costimulation of CD14 and MD-2 (Davey et al., 2008). Interestingly, major fimbriae

can exploit TLR2 signalling in order to interact with complement receptor 3 (CR3), in a novel ‘inside-out’ signalling pattern (Hajishengallis et al., 2007; Wang et al., 2007). This Ganetespib order interaction activates the binding capacity of CR3 and allows for internalization of P. gingivalis in macrophages and reduction of IL-12 production, which may collectively inhibit bacterial clearance (Hajishengallis et al., 2007). Gingipains are a group of cell surface cysteine proteinases of P. gingivalis that can also be present in secreted soluble form. They account for 85% of the total proteolytic activity of P. gingivalis (Potempa et al., 1997). Based on their substrate specificity, they are divided into arginine-specific (Arg-X) and lysine-specific (Lys-X) gingipains (Curtis et al., 2001; Guo et al., 2010). Arg-X gingipains have trypsin-like activity, and can degrade extracellular matrix components, including the integrin–fibronectin-binding, cytokine, immunoglobulin Etomidate and complement factors.

There are two types of Arg-X gingipains, namely RgpA, which contains a proteolytic and an adhesion domain, and RgpB, which contains only the proteolytic domain. There is one type of Lys-X gingipain, Kgp, which contains both a proteolytic and an adhesion domain. There are sequence similarities between the adhesion domains of Kgp and RgpA (Curtis et al., 2001). The gingipains have multiple effects on the molecular components of the immune response, and as such they can deregulate these responses. For instance, they can cleave several T-cell receptors, such as CD2, CD4 and CD8 (Kitamura et al., 2002), thereby hampering the cell-mediated immune response. They can also stimulate expression of protease-activated receptors in neutrophils (Lourbakos et al.