Sarm1/Myd88-5 Regulates Neuronal Intrinsic Immune Response to Traumatic Axonal Injuries

Traumatic injuries can trigger inflammatory reactions, leading to profound neuropathological consequences. However, the immune capacity of neurons, distinct from that of immune cells or glial cells, in response to traumatic insults remains to be fully characterized. In this study, we demonstrate that neurons can detect, cell autonomously, distant axonal damage, resulting in rapid production of a specific collection of cytokines and chemokines. This neuronal immune response appears spatially and temporally separated from injury-induced axon degeneration. We then identify through the genetic screen that this immune response is regulated by TIR-domain adaptor Sarm1/Myd88-5. We further show that Sarm1 functions through the downstream Jnk-c-Jun signal, and blockage of this Sarm1-Jnk-c-Jun pathway effectively abolishes the recruitment of immune cells to injury-afflicted neural tissues. We therefore uncover the key function of the Sarm1 signaling pathway, independent of its known role in axon degeneration, in the neuronal intrinsic immune response to traumatic axonal injuries. [Display omitted] •Neurons have an intrinsic immune capacity in response to traumatic axonal injuries•Sarm1/Myd88-5 regulates the neuronal intrinsic immune response to axonal injuries•Sarm1 functions through Jnk-c-Jun in the neuronal immune response•Sarm1-Jnk-c-Jun pathway triggers the inflammation in injury-afflicted neural tissues Wang et al. report that neurons possess an intrinsic immune capacity in response to traumatic axonal injuries, which is spatially and temporally separated from injury-induced axon degeneration. This neuronal immune response is regulated by TIR-domain adaptor protein Sarm1/Myd88-5 and its downstream Jnk-c-Jun signal.