NOD 1 in the modulation of host–microbe interactions and inflammatory bone resorption in the periodontal disease model

• Published in: Immunology Vol. 149; no. 4; pp. 374 - 385
• Main Authors: Chaves de Souza, João Antônio, Frasnelli, Sabrina Cruz Tfaile, Curylofo‐Zotti, Fabiana de Almeida, Ávila‐Campos, Mário Julio, Spolidório, Luis Carlos, Zamboni, Dario Simões, Graves, Dana T., Rossa, Carlos
• Format: Journal Article
• Language: English
• Published: 01-12-2016
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/imm.12654

Periodontitis is a chronic inflammatory condition characterized by destruction of non‐mineralized and mineralized connective tissues. It is initiated and maintained by a dysbiosis of the bacterial biofilm adjacent to teeth with increased prevalence of Gram‐negative microorganisms. Nucleotide‐binding oligomerization domain containing 1 (
NOD1
) is a member of the Nod‐like receptors (
NLR
s) family of proteins that participate in the activation of the innate immune system, in response to invading bacteria or to bacterial antigens present in the cytoplasm. The specific activating ligand for
NOD
1 is a bacterial peptidoglycan derived primarily from Gram‐negative bacteria. This study assessed the role of
NOD
1
in inflammation‐mediated tissue destruction in the context of host–microbe interactions. We used mice with whole‐genome deletion of the
NOD
1
gene in a microbe‐induced periodontitis model using direct injections of heat‐killed Gram‐negative or Gram‐negative/Gram‐positive bacteria on the gingival tissues.
In vitro
experiments using primary bone‐marrow‐derived macrophages from wild‐type and
NOD
1
knockout mice provide insight into the role of
NOD
1 on the macrophage response to Gram‐negative and Gram‐negative/Gram‐positive bacteria. Microcomputed tomography analysis indicated that deletion of
NOD
1
significantly aggravated bone resorption induced by Gram‐negative bacteria, accompanied by an increase in the numbers of osteoclasts. This effect was significantly attenuated by the association with Gram‐positive bacteria.
In vitro
, quantitative
PCR
arrays indicated that stimulation of macrophages with heat‐killed Gram‐negative bacteria induced the same biological processes in wild‐type and
NOD
1
‐deficient cells; however, expression of pro‐inflammatory mediators was increased in NOD1‐deficient cells. These results suggest a bone‐sparing role for
NOD
1
in this model.