Hm-MyD88 and Hm-SARM: two key regulators of the neuroimmune system and neural repair in the medicinal leech.

F Rodet,C Van Camp,C Boidin-Wichlacz,C Vuillaume,A Tasiemski,M Salzet,C Slomianny

doi:10.1038/srep09624

Abstract

Unlike mammals, the CNS of the medicinal leech can regenerate damaged neurites, thus restoring neural functions after lesion. We previously demonstrated that the injured leech nerve cord is able to mount an immune response promoting the regenerative processes. Indeed neurons and microglia express sensing receptors like Hm-TLR1, a leech TLR ortholog, associated with chemokine release in response to a septic challenge or lesion. To gain insights into the TLR signaling pathways involved during these neuroimmune responses, members of the MyD88 family were investigated. In the present study, we report the characterization of Hm-MyD88 and Hm-SARM. The expression of their encoding gene was strongly regulated in leech CNS not only upon immune challenge but also during CNS repair, suggesting their involvement in both processes. This work also showed for the first time that differentiated neurons of the CNS could respond to LPS through a MyD88-dependent signalling pathway, while in mammals, studies describing the direct effect of LPS on neurons and the outcomes of such treatment are scarce and controversial. In the present study, we established that this PAMP induced the relocalization of Hm-MyD88 in isolated neurons.

Highlights

Hm-myeloid differentiation factor 88 (MyD88) and Hm-sterile alpha and amardillo-motif-containing protein (SARM): Two key regulators of the neuroimmune system and neural repair in the medicinal leech
SARM consists of two sterile-alpha motif (SAM) domains that are flanked by an N-terminal Armadillo motif (ARM) and a C-terminal Toll/Il1 receptor (TIR) domain[17]
To the best of our knowledge, we clearly showed for the first time that differentiated neurons of the CNS could respond to LPS through a MyD88dependent signaling pathway

Summary

Introduction

Hm-MyD88 and Hm-SARM: Two key regulators of the neuroimmune system and neural repair in the medicinal leech. We report the characterization of Hm-MyD88 and Hm-SARM The expression of their encoding gene was strongly regulated in leech CNS upon immune challenge and during CNS repair, suggesting their involvement in both processes. TLRs are transmembrane proteins containing a Leucine-Rich Repeat (LRR) domain and a cytoplasmic Toll/Il1 receptor (TIR) domain They detect and distinguish pathogen-associated molecular patterns (PAMPs) derived from various microbial pathogens including viruses, bacteria, protozoa and fungi[2]. The second member of the MyD88 family well conserved throughout the animal kingdom is SARM It is the only TIR domain-containing adaptor conserved from C. elegans to mammals[15,16]. We report here the characterization of two members of the MyD88 family: Hm-MyD88 and Hm-SARM We demonstrated that their respective genes are tightly regulated during an immune challenge and CNS repair. A putative priming effect of MDP on TLR pathways and the possible existence of a cross talk between NLR sensor and TLRs in leech are discussed

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Results

Conclusion