Inhibition of LTA4H expression promotes Staphylococcus aureus elimination by planarians

Planarians (Platyhelminthes)—An Emerging Model Organism for Investigating Innate Immune Mechanisms

“…The inhibition of LTA4H reduces the lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines and promotes the production of cytokines, such as interleukin (IL)-10, thereby enhancing bacterial invasion or bacterial susceptibility ( Tobin et al., 2010 ; Curtis et al., 2011 ; Snelgrove, 2011 ; Tobin et al., 2012 ; Yang et al., 2014 ; Dunstan et al., 2015 ). The analysis of the publicly available transcriptome revealed the existence of S. mediterranea (Smed)-LTA4H , an ortholog to Hs-LTA4H (44% similarity at the protein level) ( Hamada et al., 2016 ). Planarian S. mediterranea is capable of clearing the Staphylococcus aureus infection, that can cause nosocomial disease, pneumonia, abscess, sepsis, and toxic shock syndrome ( Abnave et al., 2014 ).…”

“…A similar organization was found in Hydra magnipapillata (Cnidaria), where PAMP detection and antimicrobial peptide expression are possible through the communication of HvTRR1 and HvTRR2 with HvLRR1 ( Bosch et al., 2009 ). The investigations on the antimicrobial response in planarians have revealed the existence of several genes contributing to their antimicrobial defense, including Morn-2 , Traf3 , Traf6 , p38-MAPKinase , Erk , Jnk , Mkk4 , Mkk6 , Tim , Tak1 , Tab1 , JunD , Rig-1 , PGRPs , Hep , SetD8 , and LTA4H ( Abnave et al., 2014 ; Arnold et al., 2016 ; Hamada et al., 2016 ; Pang et al., 2016 ; Torre et al., 2017 ; Tsoumtsa et al., 2018 ). Most of them are orthologues of mammalian Toll-like receptor (TLR) signaling pathway components, such as Traf3 , Traf6 , p38-MAPKinase , Erk , Jnk , Mkk4 , Mkk6 , Tak1 , and Tab1 ( Song et al., 2012 ; De Nardo, 2015 ), suggesting at least partial conservation of TLR signaling pathways in planarians.…”

Culturomics revealed the bacterial constituents of the microbiota of a 10-year-old laboratory culture of planarian species S. mediterranea

“…As an example, Membrane Occupation and Recognition Nexus ( MORN ) repeat-containing-2 ( MORN2 ) has been identified to be a component of LC3 (light chain 3)-associated phagocytosis 18 . Also the role of leukotriene A4 hydrolase, a pro-inflammatory lipid mediator 21 timeless (circadian clock machinery) 22 in S. aureus clearance has been demonstrated. In-silico analysis revealed that despite the identification and characterization of the repertoire of TIR domain-containing proteins in planarian species S. mediterranea , TLRs are absent from S. mediterranea 23 , and planarian stem cells are able to drive a sensitized antibacterial response through axis PGRP-2/setd8 methyltransferase signalling 24 .…”