Human dental stem cells suppress PMN activity after infection with the periodontopathogens Prevotella intermedia and Tannerella forsythia.

Cathleen Hieke,Brigitte Müller-Hilke,Bernd Kreikemeyer,Katja Kriebel,Hermann Lang,Robby Engelmann

doi:10.1038/srep39096

Abstract

Periodontitis is characterized by inflammation associated with the colonization of different oral pathogens. We here aimed to investigate how bacteria and host cells shape their environment in order to limit inflammation and tissue damage in the presence of the pathogen. Human dental follicle stem cells (hDFSCs) were co-cultured with gram-negative P. intermedia and T. forsythia and were quantified for adherence and internalization as well as migration and interleukin secretion. To delineate hDFSC-specific effects, gingival epithelial cells (Ca9-22) were used as controls. Direct effects of hDFSCs on neutrophils (PMN) after interaction with bacteria were analyzed via chemotactic attraction, phagocytic activity and NET formation. We show that P. intermedia and T. forsythia adhere to and internalize into hDFSCs. This infection decreased the migratory capacity of the hDFSCs by 50%, did not disturb hDFSC differentiation potential and provoked an increase in IL-6 and IL-8 secretion while leaving IL-10 levels unaltered. These environmental modulations correlated with reduced PMN chemotaxis, phagocytic activity and NET formation. Our results suggest that P. intermedia and T. forsythia infected hDFSCs maintain their stem cell functionality, reduce PMN-induced tissue and bone degradation via suppression of PMN-activity, and at the same time allow for the survival of the oral pathogens.

Highlights

As part of tissue repair mechanisms, investigation on stem cell-bacteria interaction is important for better understanding of periodontal disease progression
As stem cells have immunomodulatory and tissue regenerating function[27], we aimed to demonstrate the effects human dental follicle stem cells (hDFSCs) primed by initial bacterial pathogen contact have on polymorphonuclear leukocytes (PMNs), which represent a major factor in periodontal inflammation and tissue destruction
We have shown here that both, P. intermedia and T. forsythia, trigger hDFSC IL-6 and IL-8 response, while IL-10 level remain at constant levels throughout the experiment

Summary

Introduction

As part of tissue repair mechanisms, investigation on stem cell-bacteria interaction is important for better understanding of periodontal disease progression. Human mesenchymal stem cells and gingival epithelial cells were shown to secrete IL-8 after infection with F. nucleatum and P. gingivalis in vitro[23]. Taken together it can be hypothesized that host cells, including progenitor stem cells, pathogenic bacteria and primary defense cells like PMNs, engage in interactions in the periodontal pocket. The nature of this interplay could determine periodontitis disease outcome. P. intermedia and T. forsythia were chosen for infection as only little is known about those species compared to the well-studied species P. gingivalis, A. actinomycetemcommitans and F. nucleatum Both species are tightly associated with periodontal disease[28,29], underrepresented in the current literature

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