Stingray venom activates IL-33 producing cardiomyocytes, but not mast cell, to promote acute neutrophil-mediated injury

Author(s)

dos Santos, Janaina Cardoso ; Grund, Lidiane Zito ; Seibert, Carla Simone ; Marques, Elineide Eugenio ; Soares, Anderson Brito ; Quesniaux, Valerie F. ; Ryffel, Bernhard ; Lopes-Ferreira, Monica ; Lima, Carla

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 7, AUG 11 2017.
• Web of Science Citations: 3

Abstract

One of the hallmarks of acute inflammation is neutrophil infiltration of tissues. We investigated molecular mechanisms implicated in acute neutrophilic inflammation induced by the venom of a freshwater stingray (Potamotrygon cf. henlei) in mice. Ray venom induced early mobilization of neutrophil in the microvasculature of cremaster mice and infiltration of the peritoneal cavity 2 hours after injury, in a dose-response manner. IL-1 beta, IL-6, TNF-alpha, and KC were produced. The neutrophilic infiltration did not occur in mice with ST2 receptor and MyD88 adapters neutralized, or in those with PI3K and p38 MAPK signaling blocked. Drastic reduction of neutrophil infiltration to peritoneal cavities was observed in ST2(-/-), TLR2/TLR4(-/-), MyD88(-/-), TRIF-/- and IL-17A(-/-) mice, and a partial reduction was observed in IL-18R(-/-) mice. Mast cell Kit W(sh)/W(sh)-, AHR-, NLRP3-, ICE-, IL-1 beta-, P2RX7-, CD39-, IL-17RA-, and TBX21 KO mice retain the ability to induce neutrophilia in peritoneal cavity after ray venom injection. IL- 6 and TNF-alpha alone were insufficient for promote neutrophilia in the absence of ST2 signaling. Finally, abundant production of IL-33 by cardiomyocytes was observed. These results refine our understanding of the importance of the IL-33/ST2 axis and IL-33-producing cardiomyocytes in the early acute neutrophilia induced by freshwater stingray venoms. (AU)

• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 15/12224-6 - Evaluation the mechanisms involved in the survival of long-lived antibody-secreting cells induced by IL-17- released from neutrophil extracellular traps
• Grantee: Carla Lima da Silva
• Support Opportunities: Scholarships abroad - Research
• FAPESP's process: 15/12225-2 - Evaluation the mechanisms involved in the survival of long-lived antibody-secreting cells induced by IL-17- released from neutrophil extracellular traps
• Grantee: Lidiane Zito Grund
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor