Journal Article

Entamoeba histolytica Induce Signaling via Raf/MEK/ERK for Neutrophil Extracellular Trap (NET) Formation

Carrero, Julio C., Rosales, Carlos, Alemán, Omar R., Díaz-Godínez, César, Uribe-Querol, Eileen, Fonseca, Zayda, Mora, Nancy

2018

Overview

Amoebiasis, the disease caused by is the third leading cause of human deaths among parasite infections. was reported associated with around 100 million cases of amoebic dysentery, colitis and amoebic liver abscess that lead to almost 50,000 fatalities worldwide in 2010. infection is associated with the induction of inflammation characterized by a large number of infiltrating neutrophils. These neutrophils have been implicated in defense against this parasite, by mechanisms not completely described. The neutrophil antimicrobial mechanisms include phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs). Recently, our group reported that NETs are also produced in response to trophozoites. But, the mechanism for NETs induction remains unknown. In this report we explored the possibility that leads to NETs formation via a signaling pathway similar to the pathways activated by PMA or the Fc receptor FcγRIIIb. Neutrophils were stimulated by trophozoites and the effect of various pharmacological inhibitors on amoeba-induced NETs formation was assessed. Selective inhibitors of Raf, MEK, and NF-κB prevented -induced NET formation. In contrast, inhibitors of PKC, TAK1, and NADPH-oxidase did not block -induced NETs formation. induced phosphorylation of ERK in a Raf and MEK dependent manner. These data show that activates a signaling pathway to induce NETs formation, that involves Raf/MEK/ERK, but it is independent of PKC, TAK1, and reactive oxygen species (ROS). Thus, amoebas activate neutrophils via a different pathway from the pathways activated by PMA or the IgG receptor FcγRIIIb.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Cellular and Infection Microbiology / Colitis / Degranulation / Dysentery / Entamoeba histolytica / Entamoeba histolytica - immunology / ERK / Extracellular Signal-Regulated MAP Kinases - metabolism / Extracellular Traps - metabolism / Fc receptors / Host-Pathogen Interactions / Humans / Immunoglobulin G / Kinases / Leukocytes (neutrophilic) / Microorganisms / Mitogen-Activated Protein Kinase Kinases - metabolism / Monoclonal antibodies / NAD(P)H oxidase / NETosis / NETs / neutrophil / Neutrophils / NF-κB protein / Parasites / Pathogens / Phagocytosis / Phosphorylation / Protein kinase C / Protozoa / raf Kinases - metabolism / Raf protein / Reactive oxygen species / ROS / Signal Transduction / TAK1 protein / Trophozoites / Trophozoites - immunology