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001-es BibID:	BIBFORM102500
035-os BibID:	(cikkazonosító)3600 (scopus)85126835884 (wos)000781089600001
Első szerző:	Lima, Carla
Cím:	Natterin-Induced Neutrophilia Is Dependent on cGAS/STING Activation via Type I IFN Signaling Pathway / Lima Carla, Andrade-Barros Aline Ingrid, Bernardo Jefferson Thiago Gonçalves, Balogh Eniko, Quesniaux Valerie F., Ryffel Bernhard, Lopes-Ferreira Monica
Dátum:	2022
ISSN:	1661-6596 1422-0067
Megjegyzések:	Natterin is a potent pro-inflammatory fish molecule, inducing local and systemic IL-1?/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 KO mice and partially in il-28r KO mice, but not in ifn?r KO mice. Finally, using cgas KO, sting KO, or irf3 KO 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.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Natterin neutrophilia self-DNA cGAS/STING/IRF3 pathway type I IFN signaling
Megjelenés:	International Journal Of Molecular Sciences. - 23 : 7 (2022), p. 1-15. -
További szerzők:	Andrade-Barros, Aline Ingrid Bernardo, Jefferson Thiago Gonçalves Balogh Enikő (1987-) (molekuláris biológus) Quesniaux, Valerie F. Ryffel, Bernhard Lopes-Ferreira, Monica
Pályázati támogatás:	FAPESP 2021/06084-8 Egyéb FAPESP 2019/10500-7 Egyéb FAPESP 2018/17413-0 Egyéb FAPESP 2013/07467-1 Egyéb FEDER EX016008 TARGET-Ex Egyéb FEDER EX010381 EURo-FéRI Egyéb
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