Abstract
Immune system dysregulation is increasingly being attributed to the development of a multitude of neurodegenerative diseases. This, in large part, is due to the delicate relationship that exists between neurons in the central nervous system (CNS) and peripheral nervous system (PNS), and the resident immune cells that aid in homeostasis and immune surveillance within a tissue. Classically, the inner ear was thought to be immune privileged due to the presence of a blood-labyrinth barrier. However, it is now well-established that both vestibular and auditory end organs in the inner ear contain a resident (local) population of macrophages which are the phagocytic cells of the innate-immune system. Upon cochlear sterile injury or infection, there is robust activation of these resident macrophages and a predominant increase in the numbers of macrophages as well as other types of leukocytes. Despite this, the source, nature, fate, and functions of these immune cells during cochlear physiology and pathology remains unclear. Migration of local macrophages and infiltration of bone-marrow-derived peripheral blood macrophages into the damaged cochlea occur through various signaling cascades, mediated by the release of specific chemical signals from damaged sensory and non-sensory cells of the cochlea. One such signaling pathway is CX3CL1-CX3CR1, or fractalkine (FKN) signaling, a direct line of communication between macrophages and sensory inner hair cells (IHCs) and spiral ganglion neurons (SGNs) of the cochlea. Despite the known importance of this neuron-immune axis in CNS function and pathology, until recently it was not clear whether this signaling axis played a role in macrophage chemotaxis and SGN survival following cochlear injury. In this review, we will explore the importance of innate immunity in neurodegenerative disease development, specifically focusing on the regulation of the CX3CL1-CX3CR1 axis, and present evidence for a role of FKN signaling in cochlear neuroprotection.
Highlights
The immune system is the body’s defense mechanism against pathogens and tissue injury
In a 2019 study by Finneran et al (2019), they found that central nervous system (CNS)-wide overexpression of soluble FKN via associated virus (AAV) serotype 2 (AAV2) delivery led to a rescue in cognitive function, as seen through novel recognition tasks and radial arm water maze behavior, in the same mouse model of tauopathy
Evidence in several neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Multiple sclerosis (MS), and diseases of the retina suggests FKN signaling is responsible for dampening microglia activation, resulting in neuroprotection
Summary
Department of Biomedical Sciences, School of Medicine, Creighton University, Omaha, NE, United States Reviewed by: Takayuki Okano, Kyoto University, Japan Humberto Gutierrez, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico Specialty section: This article was submitted to Cellular Neurophysiology, a section of the journal
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
