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

Autor: Franck Rodet, C. Vuillaume, C. Van Camp, Michel Salzet, Aurélie Tasiemski, Christian Slomianny, Céline Boidin-Wichlacz
Přispěvatelé: Laboratoire de Spectrométrie de Masse Biologique Fondamentale et Appliquée, Université de Lille, Sciences et Technologies, Évolution, Écologie et Paléontologie (Evo-Eco-Paleo) - UMR 8198 (Evo-Eco-Paléo (EEP)), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Évolution, Écologie et Paléontologie (Evo-Eco-Paleo) - UMR 8198 (Evo-Eco-Paléo)
Rok vydání: 2014
Předmět:
Zdroj: Scientific Reports
Scientific Reports, 2015, 5, pp.9624. ⟨10.1038/srep09624⟩
Scientific Reports, Nature Publishing Group, 2015, 5, pp.9624. ⟨10.1038/srep09624⟩
ISSN: 2045-2322
DOI: 10.1038/srep09624⟩
Popis: International audience; 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-TLR1 and Hm-MyD88 in isolated neurons. I nnate immunity corresponds to the first line of defense common to all metazoans. To sense invading pathogens , animals align a panel of germline-encoded receptors called pattern recognition receptors (PRRs) 1. Among them, the family of TLRs is the best characterized. 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 recognition of these PAMPs triggers the associated signaling pathways to activate downstream immune responses and eliminate invading pathogens 3. Among the molecules recruited by activated TLRs are the members of the MyD88 family 4. In mammals, it includes 5 adaptor proteins containing a TIR domain: myeloid differentiation factor 88 (MyD88), MyD88-adapter-like (Mal), TIR-domain-containing adaptor protein-inducing IFN beta (TRIF), TRIF-related adaptor molecule (TRAM) and sterile alpha and amardillo-motif-containing protein (SARM). All TLRs, except TLR3, recruit MyD88 to mediate innate immune signaling. MyD88 exhibits an N-terminal death domain (DD) and a C-terminal TIR domain. Upon stimulation of TLRs, MyD88 interacts with the cytosolic part of TLR through a homophilic interaction of the TIR domains. Its DD, in turn, associates with the DD of interleukin-1 receptor associated kinase (IRAK) to trigger downstream signaling cascades that lead to the activation of NF-kB 5–7. The structure of MyD88 is extremely well conserved across evolution and its key role in immunity has been demonstrated in both bilaterian and non bilaterian species 8–14. The second member of the MyD88 family particularly well conserved throughout the animal kingdom is SARM. Indeed, it is the only TIR domain-containing adaptor conserved from C. elegans to mammals 15,16
Databáze: OpenAIRE
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