Natural Killer Cells in the Orchestration of Chronic Inflammatory Diseases

Figure 4

Interaction between NK cells and the main bacterial species involved in the pathogenesis of periodontitis. Direct recognition of Fusobacterium nucleatum through NKp46 worsts periodontal disease (A). Actinobacillus actinomycetemcomitans stimulate dendritic cells that in turn elicit rapid gamma interferon responses by natural killer cells (B). P. gingivalis induces a rapidly increase of type 1 cytokine production by both dendritic cells and NK cells (C). Aggregatibacter actinomycetemcomitans induces CD2-like receptor activating cytotoxic cells (CRACC) on NK cells, via activation of dendritic cells and subsequent interleukin 12 (IL-12) signalling that results in an aggressive (D). NK cell following F. nucleatum recognition can release TNF-α that on one hand leads to tissue damage by stimulating prostaglandin E2 release from monocytes and fibroblasts and secretion of metalloproteinases that degrade extracellular matrix (ECM) proteins and on the other hand induces osteoclast differentiation and activation by increasing RANKL expression and the suppression of osteoprotegerin, a cytokine receptor that belongs to tumour necrosis factor (TNF) receptor superfamily expression in osteoblasts, resulting in alveolar bone resorption (E).