Treponema denticola in Disseminating Endodontic Infections

Treponema denticola in Disseminating Endodontic Infections
2006
F. Foschi1,2, J. Izard3, H. Sasaki1, V. Sambri4, C. Prati2, R. M?ller5, and P. Stashenko1,*
Journal of Dental Research

© 2006 International and American Associations for Dental Research

1 Department of Cytokine Biology, The Forsyth Institute, 140 The Fenway, Boston, MA 02115, USA;
2 Endodontics Unit, Department of Oral Sciences, University of Bologna, Italy;
3 Department of Molecular Genetics, The Forsyth Institute, Boston, MA, USA;
4 Section of Microbiology, DMCSS, Ospedale S. Orsola, University of Bologna, Italy; and
5 Institute for Biomedical Engineering, ETH, and University of Z?rich, Switzerland

* corresponding author, pstashenko@forsyth.org

ABSTRACT

Treponema denticola is a consensus periodontal pathogen that has recently been associated with endodontic pathology. In this study, the effect of mono-infection of the dental pulp with T. denticola and with polymicrobial "red-complex" organisms (RC) (Porphyromonas gingivalis, Tannerella forsythia, and T. denticola) in inducing disseminating infections in wild-type (WT) and severe-combined-immunodeficiency (SCID) mice was analyzed. After 21 days, a high incidence (5/10) of orofacial abscesses was observed in SCID mice mono-infected with T. denticola, whereas abscesses were rare in SCID mice infected with the red-complex organisms or in wild-type mice. Splenomegaly was present in all groups, but only mono-infected SCID mice had weight loss. T. denticola DNA was detected in the spleen, heart, and brain of mono-infected SCID mice and in the spleen from mono-infected wild-type mice, which also had more periapical bone resorption. The results indicate that T. denticola has high pathogenicity, including dissemination to distant organs, further substantiating its potential importance in oral and linked systemic conditions.

KEY WORDS: periapical lesion Ô Tannerella forsythia Ô Porphyromonas gingivalis Ô disseminating infection Ô micro-computed tomography

INTRODUCTION

The microbial etiology of endodontic disease is well-established in animal models and humans (Kakehashi et al., 1965; Sundqvist, 1994). The host immune response plays an important role in localizing these infections to the root canal space. A deficiency in antibody formation by B-lymphocytes (Teles et al., 1997; Hou et al., 2000) or in phagocytic leukocytes (Kawashima et al., 1999) results in more severe disease, including systemic dissemination with sepsis and increased mortality. Thus, the pathogenicity of endodontic bacteria is dependent upon their innate virulence as well as the hostÌs immune status.

Among oral pathogens, Treponema denticola has been associated with the severity of human periodontal diseases (Socransky et al., 1998; Yoshida et al., 2004), in association with Porphyromonas gingivalis and Tannerella forsythia, forming the so-called "red-complex" organisms (Socransky et al., 1998), and is furthermore linked to severe manifestations in immunodeficient patients (Sela, 2001). T. denticola has been linked with endodontic disease, given its association with orofacial abscesses and periapical radiolucencies (Baumgartner et al., 2003; Foschi et al., 2005; Siqueira and Rocas, 2004). Despite these relationships, the etiological role of T. denticola in endodontic disease, alone and as part of the "red complex" (Socransky et al., 1998; Rocas et al., 2001), has not yet been directly demonstrated in vivo.

The goal of the present study was therefore to determine the role of T. denticola as a mono-infection and as part of "red complex" polymicrobial infection in the etiology of endodontic disease in immunocompetent and severe combined immunodeficient (SCID) mice. The ability of each organism to disseminate in the host, and to stimulate bone resorptionÛstrong indicators of pathogenicity in the endodontic milieuÛwas also evaluated.

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