PMID- 34841314 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211130 IS - 2666-5174 (Electronic) IS - 2666-5174 (Linking) VI - 2 DP - 2021 Dec TI - Differential involvement of the canonical and noncanonical inflammasomes in the immune response against infection by the periodontal bacteria Porphyromonas gingivalis and Fusobacterium nucleatum. PG - 100023 LID - 10.1016/j.crmicr.2021.100023 [doi] LID - 100023 AB - We examined the involvement of the P2 x 7 receptor and the canonical and noncanonical inflammasomes in the control of single-species or dual-species infection by the periodontal bacteria Porphyromonas gingivalis and Fusobacterium nucleatum in cells and mice. Stimulation of the P2 x 7 receptor leads to activation of the canonical NLRP3 inflammasome and activation of caspase-1, which leads to cleavage of pro-IL-1beta to IL-1beta, a key cytokine in the host inflammatory response in periodontal disease. The non-canonical inflammasome pathway involves caspase-11. Thus, wildtype (WT), P2 x 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 P. gingivalis and/or F. nucleatum, and treated or not with extracellular ATP, which is recognized by P2 x 7. F. nucleatum infection alone promoted secretion of IL-1beta in BMDMs. Conversely, the canonical pathway involving P2 x 7 and caspase-1 was necessary for secretion of IL-1beta in BMDMs infected with P. gingivalis and in the mandible of mice coinfected with P. gingivalis and F. nucleatum. The P2 x 7 pathway can limit bacterial load in single-species and dual-species infection with P. gingivalis and F. nucleatum in BMDMs and in mice. The non-canonical pathway involving caspase-11 was required for secretion of IL-1beta induced by F. nucleatum infection in BMDMs, without treatment with ATP. Caspase-11 was also required for induction of cell death during infection with F. nucleatum and contributed to limiting bacterial load during F. nucleatum infection in BMDMs and in the gingival tissue of mice coinfected with P. gingivalis and F. nucleatum. Together, these data suggest that the P2 x 7-caspase-1 and caspase-11 pathways are involved in the immune response against infection by P. gingivalis and F. nucleatum, respectively. CI - (c) 2021 The Authors. FAU - De Andrade, Kivia Queiroz AU - De Andrade KQ AD - Immunobiology Program, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Edificio do Centro de Ciencias da Saude, Bloco G., Av. Carlos Chagas Filho, 373, Cidade Universitaria, Ilha do Fundao, Rio de Janeiro 21941-902, Brazil. FAU - Almeida-da-Silva, Cassio Luiz Coutinho AU - Almeida-da-Silva CLC AD - Immunobiology Program, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Edificio do Centro de Ciencias da Saude, Bloco G., Av. Carlos Chagas Filho, 373, Cidade Universitaria, Ilha do Fundao, Rio de Janeiro 21941-902, Brazil. AD - Department of Biomedical Sciences, University of the Pacific, Arthur A. Dugoni School of Dentistry, San Francisco, CA 94103, USA. FAU - Ojcius, David M AU - Ojcius DM AD - Department of Biomedical Sciences, University of the Pacific, Arthur A. Dugoni School of Dentistry, San Francisco, CA 94103, USA. FAU - Coutinho-Silva, Robson AU - Coutinho-Silva R AD - Immunobiology Program, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Edificio do Centro de Ciencias da Saude, Bloco G., Av. Carlos Chagas Filho, 373, Cidade Universitaria, Ilha do Fundao, Rio de Janeiro 21941-902, Brazil. LA - eng PT - Journal Article DEP - 20210223 PL - Netherlands TA - Curr Res Microb Sci JT - Current research in microbial sciences JID - 101773003 PMC - PMC8610350 OTO - NOTNLM OT - Fusobacterium nucleatum OT - Inflammasome OT - Oral cavity OT - Porphyromonas gingivalis OT - Purinergic receptor COIS- Robson Coutinho-Silva and David M. Ojcius serve on the editorial board of Current Research in Microbial Sciences. EDAT- 2021/11/30 06:00 MHDA- 2021/11/30 06:01 PMCR- 2021/02/23 CRDT- 2021/11/29 06:37 PHST- 2020/10/18 00:00 [received] PHST- 2021/01/30 00:00 [revised] PHST- 2021/02/16 00:00 [accepted] PHST- 2021/11/29 06:37 [entrez] PHST- 2021/11/30 06:00 [pubmed] PHST- 2021/11/30 06:01 [medline] PHST- 2021/02/23 00:00 [pmc-release] AID - S2666-5174(21)00004-3 [pii] AID - 100023 [pii] AID - 10.1016/j.crmicr.2021.100023 [doi] PST - epublish SO - Curr Res Microb Sci. 2021 Feb 23;2:100023. doi: 10.1016/j.crmicr.2021.100023. eCollection 2021 Dec.