Investigating the Role of CD11b in Recovery from Olfactory Injury: A Glial Perspective

Abstract

The olfactory system is comprised of multiple cells that allow an organism the sense of smell. Olfactory sensory neurons in the nasal cavity bind to odorants and transmit signals interpreted by the brain as a scent. Throughout life, this population of neurons undergoes regular cellular turnover as old neurons die, and new neurons differentiate from resident stem cells to replace them. This results in a regular accumulation of cellular debris. To combat this, the olfactory system houses phagocytic and supporting cells to maintain the environment and encourage neurogenesis. The primary cell types involved in these processes are olfactory ensheathing cells and microglia, which occupy the olfactory mucosa and olfactory bulbs respectively. The injury and recovery cycle of the olfactory system can be modelled using chemical ablation of the olfactory sensory neuron population. Our lab found that integrin CD11b was upregulated during this injury. CD11b is a complement receptor that mediates mobility and phagocytosis. By using a global CD11b-knockout mouse model, the role of CD11b in olfactory recovery was investigated through behavioral analysis, quantifying changes in microglial infiltration, glial phagocytosis, and analyzing gene expression changes in the olfactory bulbs at multiple timepoints after methimazole-induced injury. Our findings indicate CD11b removal delayed functional olfactory recovery, caused changes in olfactory glial mobility, and shifted the immune response towards a non-inflammatory reaction type. Additionally, we quantified phagocytosis of axonal debris by olfactory ensheathing cells and microglia in control and CD11b-knockout mice.