Immunologic dysfunction in the pathogenesis of periodontal diseases*

Abstract

Despite significant progress in our understanding of the pathogenesis and etiology of periodontal diseases, the nature and contribution of the immune system to this disorder remains unclear. Several studies provide evidence for either a protective or destructive rôle. These conflicting findings are difficult to reconcile, since most interpretations tend to argue for a static contributory rôle (i.e., either protective or destructive) of the immune system. Current theories on the rôle of the immune response do not address these conflicting findings as well as the contradictory observation of a detectable immune response in the face of persistent infection in these patients. In this article, we present a model, based on available data, for the contribution of the immune system to the pathogenesis of periodontal disease. This model ascribes a dynamic rôle for the immune response. As documented in other infectious diseases, it is entirely possible, for example, that a state of immunologic dysfunction may occur in the earliest stages of periodontal disease progression; this may then be followed by a period of active immune reactivity (humoral and/or cellular) that would represent either a delayed or depressed response. This model is discussed in conjunction with recent findings that several suspected periodontal pathogens are capable of producing immunosuppressive agents. Many of the apparently contradictory clinical observations concerning the host immune response to oral pathogens and its correlation (or lack of) with both the progression and severity of periodontal disease may be accounted for in this model.

The relationship between colonization and haemagglutination inhibiting and B cell epitopes of Porphyromonas gingivalis

“…In animal models P. gingivalis causes destructive disease and bone loss [2,3]. The bacterium elaborates numerous potential virulence determinants, including proteases, which may provoke or deregulate the inflammatory response in the host tissues, which in turn can lead to destructive disease [4]. In addition, in vitro studies suggest that proteases may contribute directly to destruction of host tissue [5].…”

Induction of Apoptotic Cell Death in Peripheral Blood Mononuclear and Polymorphonuclear Cells by an Oral Bacterium,Fusobacterium nucleatum

“…Increased colonization by pathogenic bacteria and subsequent modulation of host defense mechanisms in the oral cavity have been proposed to result in the initiation and progression of periodontal disease (7,27). The immunosuppressive nature of certain invasive pathogenic oral bacteria, e.g., F. nucleatum, has been reported previously (7,26,27). Inhibition of both B-and T-cell functions have also been reported in the presence of F. nucleatum (11,21,27).…”

“…There is prior evidence that bacterial species can suppress immune responses (11,22,28). In particular, F. nucleatum has been shown to inhibit many immunological functions (7,26,27). Initial observations by Shenker and Dirienzo (27) indicated significant inhibition of peripheral blood lymphocyte function by cytoplasmic extracts obtained from F. nucleatum.…”

Mechanism of internalization of the cytolethal distending toxin of Actinobacillus actinomycetemcomitans

“…The general pathogenic mechanisms and immune involvement in periodontitis, in particular the bacterial virulence factors responsible for the proposed immunosuppression in this disease, remain unclear. Studies suggest that bacterial virulence factors act to impair host defence mechanisms and play significant roles in infectious diseases associated with A. actinomycetemcomitans (Shenker, 1987;Wilson & Henderson, 1995;Henderson et al, 2003). Some cytotoxic factors produced by A. actinomycetemcomitans have been studied at the molecular level, and cytolethal distending toxin (CDT) from this pathogen has been identified and cloned (Mayer et al, 1999;Shenker et al, 1999;Sugai et al, 1998).…”