Interactions of innate and adaptive immunity in brain development and function

Abstract

It has been known for decades that the immune system has a tremendous impact on behavior. Most work has described the negative role of immune cells on the central nervous system. However, we and others have demonstrated over the last decade that a well-regulated immune system is needed for proper brain function. Here we discuss several neuro-immune interactions, using examples from brain homeostasis and disease states. We will highlight our understanding of the consequences of malfunctioning immunity on neurodevelopment and will discuss the roles of the innate and adaptive immune system in neurodevelopment and how T cells maintain a proper innate immune balance in the brain surroundings and within its parenchyma. Also, we describe how immune imbalance impairs higher order brain functioning, possibly leading to behavioral and cognitive impairment. Lastly, we propose our hypothesis that some behavioral deficits in neurodevelopmental disorders, such as in autism spectrum disorder, are the consequence of malfunctioning immunity. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease.

Keywords: Autism spectrum disorder; Innate and adaptive immunity; Microglia; Neuroimmunology; Rett; Syndrome.

Figure 1. T cells influence brain function by regulating the activation status of local myeloid cells

Top, In the T cell niche surrounding a healthy brain, T cells regulate meningeal macrophages, and possibly microglia, by the release of IL-4 and other pro-cognitive molecules. Resting microglia survey the brain parenchyma and support a healthy environment for brain development. Bottom, When T cells are absent, or malfunctioning, meningeal macrophages and microglia become activated and unleash pro-inflammatory molecules. This pro-inflammatory milieu is detrimental to normal brain function and may contribute to the developmental abnormalities in ASD.