Keiko Hirose, MD

Professor, WashU Otolaryngology

Innate immunity in the inner ear

Our lab focuses on innate immunity of the mammalian inner ear, a special sensory system that encodes sound and vibration and converts this mechanical energy into electrical impulses that are conveyed by the eighth cranial nerve to the brain.  Since 2001, our lab has studied the inflammatory response to inner ear injury and how the immune system contributes to damage and repair. The inner ear is perfused by two major networks of vessels that provide oxygen and nutrients to support the highly demanding, energy-consuming activity of hearing. The separation between the blood and inner ear fluids is maintained by tightly connected cells that reinforce this separation to ensure that small molecules, proteins, and cells remain inside the vessel lumen. The elements that form this separation in the inner ear are called the blood-labyrinth barrier (BLB). The blood labyrinth barrier and the blood brain barrier share some common traits. Like the BBB, the BLB plays an important role in regulating the entry of white blood cells from the vasculature into inner ear fluids. In cases of inflammation or injury, barrier properties change, and leukocytes adhere to the vessel wall, create gaps, leave the vessel lumen, enter the inner ear fluids, and then can eliminate infected or unwanted cells. These mononuclear phagocytes are also capable of damaging normal tissues that are not intended targets of the immune response. The goal of our research is to improve our understanding of how the immune system gains access to the inner ear, what elements of the immune system are critical for eliminating infections or limiting damage, and which of its functions contribute to damage and functional loss. 

We have arrived at an improved understanding of the dynamic nature of the blood-labyrinth barrier, the resilience of the inner ear to changes in barrier permeability, the role of macrophages in altering inner ear barrier permeability, and the important role of chemokine receptors as modulators of cochlear monocytes and macrophages and their impact on inner ear function. Our current work focuses on blood labyrinth barrier properties and how congenital cytomegalovirus infection and the immune response to viral infection affect inner ear development and function. We use a mouse model of congenital CMV spread hematogenously that replicates the human condition closely.  Our goal is to arrive at new targets for therapy to improve hearing preservation in infants and children exposed to congenital viral infection.  My research focus in cochlear inflammation and background as a pediatric otolaryngologist both contribute significantly to my interest in these questions. 

More about the Hirose lab