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

Abstract

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.

Physical and mechanical regulation of macrophage phenotype and function

“…5) Last but not least, immune cells including macrophages are notorious for being very heterogeneous. The ground state activation level of macrophages is known to fluctuate depending on time of the day, seasons of the year, diet and systemic conditions of the host 93 , which may explain inconsistencies in studies using primary cells.…”

Recent advances in vertebrate and invertebrate transgenerational immunity in the light of ecology and evolution

“…Little knowledge exists about epigenetic mechanisms that could potentially regulate host−pathogen interactions and the development of host immune defense strategies (Gómez-Díaz et al 2012). Numerous studies indicate that epigenetic mechanisms fulfill a crucial role in regulating the transcription of immune-related genes upon infections (Huang and Wells 2014;Marr et al 2014;Okamoto et al 2014;Smale et al 2014). Pathogen exposure of the parental generation might mediate epigenetic marks that could be passed on as protective cues to the offspring and subsequent generations.…”

In vivo immune signatures of healthy human pregnancy: Inherently inflammatory or anti-inflammatory?

“…Attention needs to be given to (i) understanding maternal adaptations and (ii) creating a biological definition of an optimal pregnancy phenotype from fetal, maternal and paternal standpoints. Understanding putative changes in women’s in vivo innate immune status during normal pregnancy–the healthy phenotype–will strengthen efforts to understand linkages between in vivo maternal status and the subsequent development of healthy vs. chronic inflammatory phenotypes such as asthma or autoimmunity in children, or their mothers, later in life [9–13]. …”