TREM2 and Inflammatory Regulation of Microglial Functions Over the Lifespan and Across Species

The proper development and function of the mammalian central nervous system (CNS) depend critically on the activity of the immune cells referred to as microglia. The microglia are the resident macrophages of the CNS and act as the primary immune regulators in the CNS during normal development, adult tissue homeostasis, and in injury and disease. In this thesis, we discuss the exciting developments in our understanding of microglial biology from their in vivo developmental origin, to their participation in CNS homeostasis and pathophysiological states, such as systemic inflammation induced by Lipopolysaccharide (LPS), and neurodegeneration due to aging. We will also look at ex vivo microglial response to S. aureus and Synaptosomes. Then describe the in vitro development and maturation of human microglial-like cells (iMGL) differentiated from hematopoietic progenitor cells (iHPCs). And finally we will show the CNS immune response to the inhalation of fine aerosolized particulates of a common fungus Alternaria. We see that microglia are a versatile cell and possess the capacity to morphologically and functionally adapt to their ever-changing environment. Even in a resting state, the processes of microglia are highly dynamic and perpetually scan the CNS. Studies of microglial development, homeostasis, and function give us insights into how to modulate them during the course of CNS diseases. Importantly, we now have the technologies to study human microglial function in a pure in vitro setting, which should vastly enhance our understanding of these cells and how various mutations contribute to altered functions