Activation of inflammasomes in dendritic cells and macrophages by Mycoplasma salivarium

Abstract

Interleukin-1β (IL-1β) plays crucial roles in the pathogenesis of periodontal disease. It is produced after the processing of pro-IL-1β by caspase-1, which is activated by the inflammasome-a multiprotein complex comprising nucleotide-binding domain leucine-rich repeat-containing receptor (NLR), the adaptor protein apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), and procaspase-1. Mycoplasma salivarium preferentially inhabits the gingival sulcus and the incidence and number of organisms in the oral cavity increase significantly with the progression of periodontal disease. To initially clarify the association of this organism with periodontal diseases, this study determined whether it induces IL-1β production by innate immune cells such as dendritic cells or macrophages by using Mycoplasma pneumoniae as a positive control. Both live and heat-killed M. salivarium and M. pneumoniae cells induced IL-1β production by XS106 murine dendritic cells as well as pyroptosis. The activities were significantly downregulated by silencing of caspase-1. Bone-marrow-derived macrophage (BMMs) from wild-type and NLR-containing protein 3 (NLRP3)-, ASC-, and caspase-1-deficient mice were examined for IL-1β production in response to these mycoplasmas. Live M. salivarium and M. pneumoniae cells almost completely lost the ability to induce IL-1β production by BMMs from ASC- and caspase-1-deficient mice. Their activities toward BMMs from NLRP3-deficient mice were significantly but not completely attenuated. These results suggest that live M. salivarium and M. pneumoniae cells can activate several types of inflammasomes including the NLRP3 inflammasome. Both M. salivarium and M. pneumoniae cells can activate THP-1 human monocytic cells to induce IL-1β production. Hence, the present finding that M. salivarium induces IL-1β production by dendritic cells and macrophages may suggest the association of this organism with periodontal diseases.

Keywords: Mycoplasma pneumoniae; Mycoplasma salivarium; inflammasome; interleukin-1β; nucleotide-binding domain leucine-rich repeat-containing receptor-containing protein 3.