We examined the involvement of the P2 × 7 receptor and the canonical and noncanonical inflammasomes in the control of single-species or dual-species infection by the periodontal bacteria and in cells and mice. Stimulation of the P2 × 7 receptor leads to activation of the canonical NLRP3 inflammasome and activation of caspase-1, which leads to cleavage of pro-IL-1β to IL-1β, a key cytokine in the host inflammatory response in periodontal disease. The non-canonical inflammasome pathway involves caspase-11. Thus, wildtype (WT), P2 × 7, caspase-11 and caspase-1/11 mice were co-infected with both bacterial species. In parallel, bone marrow-derived macrophages (BMDMs) from WT mice and the different knockout mice were infected with and/or , and treated or not with extracellular ATP, which is recognized by P2 × 7. infection alone promoted secretion of IL-1β in BMDMs. Conversely, the canonical pathway involving P2 × 7 and caspase-1 was necessary for secretion of IL-1β in BMDMs infected with and in the mandible of mice coinfected with and . The P2 × 7 pathway can limit bacterial load in single-species and dual-species infection with and in BMDMs and in mice. The non-canonical pathway involving caspase-11 was required for secretion of IL-1β induced by infection in BMDMs, without treatment with ATP. Caspase-11 was also required for induction of cell death during infection with and contributed to limiting bacterial load during infection in BMDMs and in the gingival tissue of mice coinfected with and . Together, these data suggest that the P2 × 7-caspase-1 and caspase-11 pathways are involved in the immune response against infection by and , respectively.