Contribution of circulating monocytes in maintaining homeostasis of resident macrophages in postnatal and young adult mouse cochlea

Abstract

The percentage of macrophage subpopulations based on their origins in the adult cochlea remains unclear. This study aimed to elucidate the origins of cochlear macrophages during the onset phase and development of auditory function. We used three types of mice: wildtype ICR mice, colony-stimulating factor 1 receptor (Csf1r)-deficient mice, and Ms4a3Cre-Rosa tdTomato (Ms4a3tdT) transgenic mice. Macrophages were labeled with ionized calcium-binding adapter molecule 1 (Iba1), which is specific to more mature macrophages, and CD11b, which is specific to monocyte lineage. We investigated the spatial and temporal distribution patterns of resident macrophages in the cochlea during the postnatal and early adult stages. During the adult stages, the rate of monocytes recruited from the systemic circulation increased; moreover, Iba1+/CD11b− cochlear macrophages gradually decreased with age. Fate mapping of monocytes using Ms4a3tdT transgenic mice revealed an increased proportion of bone marrow-derived cochlear macrophages in the adult stage. Contrastingly, the proportion of yolk sac- and fetal liver-derived tissue-resident macrophages decreased steadily with age. This heterogeneity could be attributed to differences in environmental niches within the tissue or at the sub-tissue levels. Future studies should investigate the role of cochlear macrophages in homeostasis, inflammation, and other diseases, including infection, autoimmune, and metabolic diseases.

Temporal bone marrow of the rat and its connections to the inner ear

“…Experiments have shown that innate immune cells enter the perilymph through the spiral ligament ( 67 ) whereas lymphocytes enter through modiolar venules ( 68 ). Moreover, lateral wall macrophages (and a subpopulation of spiral ligament fibrocytes) derive from bone marrow cells ( 69–71 ) and the proportion of bone marrow-derived macrophages increases with age ( 72 ). Our data would support a local bone marrow production of innate cells reaching the lateral wall, as in the brain ( 48 ), since both CAEM and VEM are connected to the spiral ligament and external cochlear wall but not to the cochlear modiolus.…”

Macrophages in the Inner Ear: Discoveries and Innovative Techniques Illustrating Their Key Roles in Homeostasis and Inflammation

“…Macrophages in the Inner Ear: Discoveries and Innovative Techniques Illustrating Their Key… DOI: http://dx.doi.org/10.5772/intechopen.1005106 Some studies have shown that inner ear macrophages can also arise from resident precursor cells in the inner ear [7,17].…”

“…population that is regularly renewed by monocytes in the bloodstream [7,18]. In the stria vascularis of the mature cochlea, resident macrophages can be distinguished by the expression of markers, such as F4/80, CD68, Iba1, and CD11b [18][19][20], and they are primarily positioned close to blood vessels, serving as perivascular macrophages (PVMs).…”

“…However, recent studies have shown that inner ear macrophages do exist and play essential roles in the inner ear [3,4]. These cells have been shown to be present in the spiral ganglion, spiral ligament, and stria vascularis of the inner ear [3,[5][6][7]. The origin and distribution of these macrophages within the inner ear are linked to their functions, which are not yet entirely understood [8].…”