The Ground State of Innate Immune Responsiveness Is Determined at the Interface of Genetic, Epigenetic, and Environmental Influences

Monocytes and macrophages form the major cellular component of the innate immune system, with roles in tissue development, homeostasis, and host defense against infection. Environmental factors were shown to play a significant part in determining innate immune responsiveness, and this included systemic conditions, such as circulating glucose levels, gut microflora, time of year, and even diurnal rhythm, which had a direct impact on innate immune receptor expression. Although the underlying molecular processes are just beginning to emerge, it is clear that environmental factors may alter epigenetic states of peripheral blood monocytes and resident tissue macrophages. We conclude that some measure of cellular ground state must become an essential part of the analysis of myeloid responsiveness or infectious susceptibility.