Early life environment and developmental immunotoxicity in inflammatory dysfunction and disease

Abstract

Components of the innate immune system such as macrophages and dendritic cells are instrumental in determining the fate of immune responses and are, also, among the most sensitive targets of early life environmental alterations including developmental immunotoxicity (DIT). DIT can impede innate immune cell maturation, disrupt tissue microenvironment, alter immune responses to infectious challenges, and disrupt regulatory responses. Dysregulation of inflammation, such as that observed with DIT, has been linked with an increased risk of chronic inflammatory diseases in both children and adults. In this review, we discuss the relationship between early-life risk factors for innate immune modulation and promotion of dysregulated inflammation associated with chronic inflammatory disease. The health risks from DIT-associated inflammation may extend beyond primary immune dysfunction to include an elevated risk of several later-life, inflammatory-mediated diseases that target a wide range of physiological systems and organs. For this reason, determination of innate immune status should be an integral part of drug and chemical safety evaluation.

Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases

“…The term "developmental immunotoxicity" has been coined to describe permanent modifications to the immune function that take place early in life, leading to later development of allergies, asthma, and autoimmune diseases [278][279][280]. These authors have argued that prenatal and/or early life exposure to environmental toxins can lead to a phenotype that includes a hyperinflammatory response and disruption of cytokine networks, and they propose that an increased exposure to environmental toxins early in life may contribute to the increased incidence of these conditions observed today.…”

The Completed Self: An Immunological View of the Human-Microbiome Superorganism and Risk of Chronic Diseases

“…Recently, the role of DIT, innate immune cell development and risk of inappropriate inflammation were reviewed by Leifer and Dietert [128]. Major developmental immunotoxicants such as the heavy metals, lead, mercury, and cadmium and dioxin are known to impact innate immune cell responses to challenge and to promote inappropriate inflammatory responses leading to tissue damage.…”

Effects of Endocrine Disrupters on Immune Function and Inflammation

“…Several factors change, starting with innate immune cells and ending with inappropriately directed and/or unresolving inflammation in tissues [44]. Lead exposure can produce elevated arachidonate on cell surfaces, which contributes to elevated prostaglandin production [45] and elevated reactive oxygen species production by innate immune cells [46].…”