Cochlear supporting cells function as macrophage-like cells and protect audiosensory receptor hair cells from pathogens

Yushi Hayashi,Hidenori Suzuki,Ikuno Uehara,Mitsutoshi Yoneyama,Takashi Fujita,Atsuko Tanimura,Shin-Ichiro Kitajiri,Naoto Koyanagi,Hiroki Kato,Wataru Nakajima,Koji Onomoto,Satoshi Koike,Toshiki Himeda,Tatsuya Katsuno,Yasushi Kawaguchi,Nobuyuki Tanaka

doi:10.1038/s41598-020-63654-9

Abstract

To protect the audiosensory organ from tissue damage from the immune system, the inner ear is separated from the circulating immune system by the blood-labyrinth barrier, which was previously considered an immune-privileged site. Recent studies have shown that macrophages are distributed in the cochlea, especially in the spiral ligament, spiral ganglion, and stria vascularis; however, the direct pathogen defence mechanism used by audiosensory receptor hair cells (HCs) has remained obscure. Here, we show that HCs are protected from pathogens by surrounding accessory supporting cells (SCs) and greater epithelial ridge (GER or Kölliker’s organ) cells (GERCs). In isolated murine cochlear sensory epithelium, we established Theiler’s murine encephalomyelitis virus, which infected the SCs and GERCs, but very few HCs. The virus-infected SCs produced interferon (IFN)-α/β, and the viruses efficiently infected the HCs in the IFN-α/β receptor-null sensory epithelium. Interestingly, the virus-infected SCs and GERCs expressed macrophage marker proteins and were eliminated from the cell layer by cell detachment. Moreover, lipopolysaccharide induced phagocytosis of the SCs without cell detachment, and the SCs phagocytosed the bacteria. These results reveal that SCs function as macrophage-like cells, protect adjacent HCs from pathogens, and provide a novel anti-infection inner ear immune system.

Highlights

To protect the audiosensory organ from tissue damage from the immune system, the inner ear is separated from the circulating immune system by the blood-labyrinth barrier, which was previously considered an immune-privileged site
A recent study reported that ionized calcium-binding adapter molecule 1 (Iba1)-positive resident macrophages were present in high numbers in the spiral ligament, spiral ganglion, and stria vascularis of the postnatal cochlea in mice[12]
Infections with Theiler’s murine encephalomyelitis virus (TMEV) were mainly established in supporting cells (SCs), and infections in hair cells (HCs) were rarely observed from 9 h post-infection (Fig. 1b, left)

Summary

Introduction

To protect the audiosensory organ from tissue damage from the immune system, the inner ear is separated from the circulating immune system by the blood-labyrinth barrier, which was previously considered an immune-privileged site. Recent studies have shown that macrophages are distributed in the cochlea, especially in the spiral ligament, spiral ganglion, and stria vascularis; the direct pathogen defence mechanism used by audiosensory receptor hair cells (HCs) has remained obscure. In the mammalian inner ear, audiosensory receptor hair cells (HCs) are located over the basilar membrane in the organ of Corti, which vibrates in response to sound waves[3]. A recent study using bone marrow chimeric mice showed that macrophages are present in the spiral ligament and spiral ganglion, but not in the sensory epithelium[19] This suggests that there is a mechanism to prevent infectious agents such as viruses entering the organ of Corti. The defence mechanism around HCs when pathogens invade beyond these lines of defence awaits elucidation

Methods

Results

Conclusion