Environmental toxicants and the developing immune system: A missing link in the global battle against infectious disease?

Abstract

There is now compelling evidence that developmental exposure to chemicals from our environment contributes to disease later in life, with animal models supporting this concept in reproductive, metabolic, and neurodegenerative diseases. In contrast, data regarding how developmental exposures impact the susceptibility of the immune system to functional alterations later in life are surprisingly scant. Given that the immune system forms an integrated network that detects and destroys invading pathogens and cancer cells, it provides the body's first line of defense. Thus, the consequences of early-life exposures that reduce immune function are profound. This review summarizes available data for pollutants such as cigarette smoke and dioxin-like compounds, which consistently support the idea that developmental exposures critically impact the immune system. These findings suggest that exposure to common chemicals from our daily environment represent overlooked contributors to the fact that infectious diseases remain among the top five causes of death worldwide.

SExual Epigenetic Dimorphism in The Human Placenta: Implications for Susceptibility During The Prenatal Period

“…Specifically, immune-related TLR7 was shown to be hypermethylated in males relative to females and TLR8 was hypomethylated in males as compared with females. These immune-related differences between the male and female placental methylomes may contribute to differential susceptibility to environmental exposures between the sexes [8]. For example, an enhanced capability for transporting toxicants across the placenta in males during the prenatal period may be accounted for by differences in activation of the placental transporter voltage-dependent anion-selective channel protein 1, a major calcium transport channel [55] critical for fetal development.…”

“…In contrast to these essential functions, the placenta also serves as a source of exposure for toxic substances, dysregulated hormone signaling and immune-related proteins [2]. Such exposures including maternal stress, excess hormones, cytokines or environmental toxicants impact fetal health and influence later-life health outcomes [3][4][5][6][7][8][9][10][11].…”

Prenatal exposure to bisphenol A and phthalates and childhood respiratory tract infections and allergy

“…2 Certain pollutants have been suggested to affect susceptibility to infections and development of allergy and asthma during the first years of life, including compounds commonly used in plastic manufacture. 1,2 In recent years, researchers have focused on bisphenol A (BPA) and phthalates because of their potential immunomodulatory capacities 3,4 and the possible effects of these compounds on the development of the respiratory system during fetal life. 5 BPA and phthalates are produced and used in large quantities worldwide and are present in a wide range of consumer products, including cosmetics, plastics, carpets, building materials, toys, and cleaning products.…”

Activation of the aryl hydrocarbon receptor during development enhances the pulmonary CD4+ T-cell response to viral infection

“…Although less extensively probed, several studies indicate that AHR signaling also influences the development of the immune system (9,24). Moreover, inappropriate AHR activation during development alters immune responses in the adult offspring, although the majority of these effects have been characterized outside of the lung (e.g., lymphoid organs and blood) (44). A subset of these reports showed persistent changes in host responses to infection in developmentally exposed offspring (6,21,39,41), yet effects on responses in the lung during infection have not been fully investigated.…”