{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:40:36Z","timestamp":1785307236848,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T00:00:00Z","timestamp":1648166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004794","name":"French National Centre for Scientific Research","doi-asserted-by":"publisher","award":["FEDER EX016008 TARGET-Ex and EX010381 EURo-F\u00e9RI"],"award-info":[{"award-number":["FEDER EX016008 TARGET-Ex and EX010381 EURo-F\u00e9RI"]}],"id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Natterin is a potent pro-inflammatory fish molecule, inducing local and systemic IL-1\u03b2\/IL-1R1-dependent neutrophilia mediated by non-canonical NLRP6 and NLRC4 inflammasome activation in mice, independent of NLRP3. In this work, we investigated whether Natterin activates mitochondrial damage, resulting in self-DNA leaks into the cytosol, and whether the DNA sensor cGAS and STING pathway participate in triggering the innate immune response. Employing a peritonitis mouse model, we found that the deficiency of the tlr2\/tlr4, myd88 and trif results in decreased neutrophil influx to peritoneal cavities of mice, indicative that in addition to MyD88, TRIF contributes to neutrophilia triggered by TLR4 engagement by Natterin. Next, we demonstrated that gpcr91 deficiency in mice abolished the neutrophil recruitment after Natterin injection, but mice pre-treated with 2-deoxy-d-glucose that blocks glycolysis presented similar infiltration than WT Natterin-injected mice. In addition, we observed that, compared with the WT Natterin-injected mice, DPI and cyclosporin A treated mice had a lower number of neutrophils in the peritoneal exudate. The levels of dsDNA in the supernatant of the peritoneal exudate and processed IL-33 in the supernatant of the peritoneal exudate or cytoplasmic supernatant of the peritoneal cell lysate of WT Natterin-injected mice were several folds higher than those of the control mice. The recruitment of neutrophils to peritoneal cavity 2 h post-Natterin injection was intensely impaired in ifnar\u00a0KO mice and partially in il-28r\u00a0KO mice, but not in ifn\u03b3r\u00a0KO mice. Finally, using cgas\u00a0KO, sting\u00a0KO, or irf3\u00a0KO mice we found that recruitment of neutrophils to peritoneal cavities was virtually abolished in response to Natterin. These findings reveal cytosolic DNA sensors as critical regulators for Natterin-induced neutrophilia.<\/jats:p>","DOI":"10.3390\/ijms23073600","type":"journal-article","created":{"date-parts":[[2022,3,27]],"date-time":"2022-03-27T21:27:51Z","timestamp":1648416471000},"page":"3600","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Natterin-Induced Neutrophilia Is Dependent on cGAS\/STING Activation via Type I IFN Signaling Pathway"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8161-966X","authenticated-orcid":false,"given":"Carla","family":"Lima","sequence":"first","affiliation":[{"name":"Immunoregulation Unit of the Laboratory of Applied Toxinology (CETICs\/FAPESP), Butantan Institute, Vital Brazil Avenue, S\u00e3o Paulo 05503-009, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline Ingrid","family":"Andrade-Barros","sequence":"additional","affiliation":[{"name":"Immunoregulation Unit of the Laboratory of Applied Toxinology (CETICs\/FAPESP), Butantan Institute, Vital Brazil Avenue, S\u00e3o Paulo 05503-009, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jefferson Thiago Gon\u00e7alves","family":"Bernardo","sequence":"additional","affiliation":[{"name":"Immunoregulation Unit of the Laboratory of Applied Toxinology (CETICs\/FAPESP), Butantan Institute, Vital Brazil Avenue, S\u00e3o Paulo 05503-009, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eniko","family":"Balogh","sequence":"additional","affiliation":[{"name":"MTA-DE Lend\u00fclet Vascular Pathophysiology Research Group, Research Centre for Molecular Medicine, Faculty of Medicine, University of Debrecen, 4027 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie F.","family":"Quesniaux","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Immunology and Neurogenetics (INEM), UMR7355, CNRS and University of Orl\u00e9ans, 45071 Orl\u00e9ans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2897-8230","authenticated-orcid":false,"given":"Bernhard","family":"Ryffel","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Immunology and Neurogenetics (INEM), UMR7355, CNRS and University of Orl\u00e9ans, 45071 Orl\u00e9ans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Lopes-Ferreira","sequence":"additional","affiliation":[{"name":"Immunoregulation Unit of the Laboratory of Applied Toxinology (CETICs\/FAPESP), Butantan Institute, Vital Brazil Avenue, S\u00e3o Paulo 05503-009, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.biochi.2005.12.008","article-title":"Transcriptome analysis of expressed sequence tags from the venom glands of the fish Thalassophryne nattereri","volume":"88","author":"Lorenzini","year":"2006","journal-title":"Biochimie"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.biochi.2005.03.016","article-title":"Natterins, a new class of proteins with kininogenase activity characterized from Thalassophryne nattereri fish venom","volume":"87","author":"Spencer","year":"2005","journal-title":"Biochimie"},{"key":"ref_3","first-page":"2151","article-title":"Kininogenase activity of Thalassophryne nattereri fish venom","volume":"11","author":"Emim","year":"2004","journal-title":"Biochem. 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