It could, therefore, be hypothesized

that P. gingivalis modulate T-cell development and function in ways that promotes Th17-mediated inflammation Doxorubicin supplier over a Th1-dependent cell-mediated immune response, which is thought to promote clearance of P. gingivalis [60]. Numerous Th17 cells can be observed in periodontitis lesions [93] and can function as an osteoclastogenic subset that links T-cell activation to inflammatory bone loss [98, 99]. On the other hand, Th1 cells are thought to play a protective role in periodontitis [100], although some studies have attributed destructive effects to Th1 cells [101]. Overall, more research is warranted to better understand the roles of T-cell subsets in periodontitis and the biological relevance of their modulation by P. gingivalis in the context of its role as a keystone pathogen. In inflammatory conditions associated with bacterial communities, traditional concepts of pathogen selleck kinase inhibitor and commensal have become obsolete. This is well illustrated by periodontal disease where P. gingivalis can remain quiescent for long periods of time before (and after)

expressing pathogenicity through manipulation of the host response and disruption of homeostasis. Conversely, organisms usually considered commensals, such as S. gordonii, can act as accessory pathogens and elevate the pathogenicity of P. gingivalis. Commensal organisms can also act as pathobionts, i.e. following homeostasis breakdown and initiation of inflammation, these commensals-turned pathogens can propagate and amplify destructive periodontal inflammation. In this regard, a recent study identified a bacterium (designated NI1060) in the murine oral cavity that selectively accumulates in damaged periodontal tissue and causes inflammatory

bone loss by activating the intracellular PRR Nod1 [102]. NI1060 appears to thrive over under inflammatory conditions, apparently because it can readily procure nutrients derived from tissue breakdown in an inflammatory environment. NI1060, moreover, contributes to the exacerbation of inflammation by inducing neutrophil-specific chemokines, thereby augmenting neutrophil infiltration in the periodontal tissue [102]. Other commensals (NI440 and NI968) dominate exclusively in healthy sites and do not behave as periodontal pathobionts [102]. The notion that there are pathobionts that can opportunistically contribute to periodontitis is consistent with recent metagenomic studies showing a strong association of previously underappreciated bacteria (including the gram-positive Filifactor alocis and Peptostreptococcus stomatis and other species from the genera Prevotella, Megasphaera, Selenomonas, and Desulfobulbus) with periodontitis [8, 103, 104]. Moreover, as the bacterial biomass increases with increasing periodontal inflammation, the ecological shift from health to disease involves the emergence of newly dominant community members as opposed to the appearance of novel species [8].