Direct Recognition of Fusobacterium nucleatum by the NK Cell Natural Cytotoxicity Receptor NKp46 Aggravates Periodontal Disease

PLoS Pathogens

David Polak¹  Asaf Wilensky¹  Stella Chaushu¹  Gilad Bachrach¹  Lior Shapira¹  Ofer Mandelboim²  Moran Elboim²  Gili Halftek²  Hagit Achdout²  Chamutal Gur² 

[1] Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel;Lautenberg Center of General and Tumor Immunology, Hebrew University –Hadassah School of Medicine, IMRIC, Jerusalem, Israel

关键词: NK cells;    Secretion;    Alveolar bone;    Periodontitis;    Immune cells;    Cytokines;    Inflammatory diseases;    Proteases;   

DOI  :  10.1371/journal.ppat.1002601

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Periodontitis is a common human chronic inflammatory disease that results in the destruction of the tooth attachment apparatus and tooth loss. Although infections with periopathogenic bacteria such as Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum) are essential for inducing periodontitis, the nature and magnitude of the disease is determined by the host's immune response. Here, we investigate the role played by the NK killer receptor NKp46 (NCR1 in mice), in the pathogenesis of periodontitis. Using an oral infection periodontitis model we demonstrate that following F. nucleatum infection no alveolar bone loss is observed in mice deficient for NCR1 expression, whereas around 20% bone loss is observed in wild type mice and in mice infected with P. gingivalis. By using subcutaneous chambers inoculated with F. nucleatum we demonstrate that immune cells, including NK cells, rapidly accumulate in the chambers and that this leads to a fast and transient, NCR1-dependant TNF-α secretion. We further show that both the mouse NCR1 and the human NKp46 bind directly to F. nucleatum and we demonstrate that this binding is sensitive to heat, to proteinase K and to pronase treatments. Finally, we show in vitro that the interaction of NK cells with F. nucleatum leads to an NCR1-dependent secretion of TNF-α. Thus, the present study provides the first evidence that NCR1 and NKp46 directly recognize a periodontal pathogen and that this interaction influences the outcome of F. nucleatum-mediated periodontitis.

【 授权许可】

CC BY