The Ancestral Environment Shapes Antiviral CD8+ T cell Responses across Generations

Abstract

SummaryRecent studies have linked health fates of children to environmental exposures of their great grandparents. However, few studies have considered whether ancestral exposures influence immune function across generations. Here, we report transgenerational inheritance of altered T cell responses resulting from maternal (F0) exposure to the aryl hydrocarbon receptor ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Since F0 exposure to TCDD has been linked to transgenerational transmission of reproductive problems, we asked whether maternal TCDD exposure also caused transgenerational changes in immune function. F0 exposure caused transgenerational effects on the CD8+ T cell response to influenza virus infection in females but not in males. Outcrosses showed changes were passed through both parental lineages. These data demonstrate that F0 exposure to an aryl hydrocarbon receptor (AHR) agonist causes durable changes to immune responses that can affect subsequent generations. This has broad implications for understanding how the environment of prior generations shapes susceptibility to pathogens and antiviral immunity in later generations.

Developmental 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin exposure of either parent enhances the risk of necrotizing enterocolitis in neonatal mice

“…Unexpectedly, localization of macrophages to ilea of F2P TCDD and F2M TCDD pups was highly variable and appeared to be independent of diet as well as disease state (Figure 4). Several studies have reported multigenerational and transgenerational alterations in immune system development as a consequence of developmental or ancestral TCDD exposure (Post et al, 2019; Vorderstrasse, Cundiff, & Lawrence, 2004). Thus, the variable macrophage response of our F2P TCDD and F2M TCDD pups may reflect similar immune impairments due to their parental TCDD exposure.…”

“…TCDD is a ubiquitous environmental toxicant and multiple studies have found that in utero exposure negatively impacts immune system development (Lawrence & Vorderstrasse, 2013). For example, Post et al (2019) reported adult mice with a direct or ancestral history of TCDD exposure exhibited an impaired ability to clear influenza infection while Peltier et al reported similarly exposed mice exhibit an inflammatory phenotype during pregnancy (Peltier et al, 2013). Our previous studies demonstrated that adult male and female F1 TCDD animals consistently demonstrate a heightened inflammatory response to either viral or bacterial challenges (Ding et al, 2011; Ding et al, 2018).…”

“…Among persistent environmental toxicants associated with combustion, 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin ([TCDD], or commonly, dioxin) is known to be a potent an AhR agonist. Lawrence and colleagues have recently shown that developmental exposure to TCDD alters the adult immune response across multiple generations (Post et al, 2019). Importantly, several studies have identified TCDD in human cord blood (Ataniyazova et al, 2001; Morokuma, Tsukimori, Hori, Kato, & Furue, 2017), indicating the occurrence of a developmental exposure with the potential to negatively affect neonatal and adult health (Mallozzi, Bordi, Garo, & Caserta, 2016).…”

DNA Methylation Patterns in CD4+ T Cells of Naïve and Influenza A Virus-Infected Mice Developmentally Exposed to an Aryl Hydrocarbon Receptor Ligand

“…To detect effector proteins, cells were incubated in the presence of recombinant mouse interleukin-2 (IL-2; R&D Systems) and brefeldin A (Sigma-Aldrich) for 1 h at 37°C prior to CD16/32 mAb block or extracellular antibody staining. Anti-CD107a [LAMP-1 (lysosomal-associated membrane protein 1)] was added, and the cells were incubated for an additional 4 h at 37°C prior to extracellular staining ( Post et al. 2019 ).…”

Semen Quality as a Potential Susceptibility Indicator to SARS-CoV-2 Insults in Polluted Areas<strong> </strong>

“…Moreover, environmental pollutants can increase susceptibility to non-communicable diseases (NCDs) and determine a significant decline in body's defences, possibly due to also transgenerational effects that may partly explain the worldwide disease burden consisting not only in non-communicable but also communicable diseases (dengue, yellow fever, tuberculosis, etc.) [24][25][26][27][28][29][30][31][32][33][34][35][36] . Furthermore, it shows that this is transmitted to the following generations, by reducing the defence ability toward viral pathogens 26 .…”