FEWER T LYMPHOCYTES AND DECREASED PULMONARY INFLUENZA VIRUS BURDEN IN MICE EXPOSED TO 2,3,7,8-TETRACHLORODIBENZO-p-DIOXIN (TCDD)

Abstract

The immune system is a sensitive target for the toxicity of the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In mice, immunotoxicity associated with exposure to TCDD includes suppression of humoral and cell-mediated immunity and impaired host resistance to infectious agents. However, the underlying mechanisms for these effects of TCDD are unknown. We previously reported that treatment of C57BI/6 mice with TCDD and influenza A virus increases mortality, impairs cytokine production, and suppresses T cell expansion and the generation of cytotoxic T lymphocytes (CTL) in the draining lymph node. However, the overall virus-specific cytolytic activity in the lung is unaffected. This enigmatic finding left several questions unanswered, including whether decreased CD8+ lymphocytes in the lung are the consequence of either delayed or suppressed recruitment of cells to the lung; whether exposure to TCDD affects the recruitment of CD4+ cells to the lung; and what effect TCDD treatment has on pulmonary virus burden. To compare the kinetics of the response in vehicle- and TCDD-treated mice, we examined the number of bronchoalveolar lavage (BAL) cells and CTL activity in the lung through d 10 postinfection. We found that the peak day for cellular influx and cytolytic activity in the lung is 9 d after infection. Immunophenotypic analysis of BAL cells shows that, when compared with BAL cells from infected controls, exposure to TCDD caused a 50% decrease in the percentage and number of both CD4+ and CD8+ cells. When the pulmonary virus burden was examined over time, we found that on d 1-5 postinfection, lungs from mice exposed to TCDD generally had lower virus titers than lung homogenates from vehicle-treated controls. By d 9 postinfection, no influenza virus was detected in lung homogenates from either vehicle- or TCDD-treated mice. These findings are likely not related to the observed decrease in CD4+ and CD8+ BAL cells; moreover, the diminished CD4+ population in the lung indicates that CD4+ cells are probably not compensating for the decreased CTL generation in TCDD-treated mice. Our observation that mice exposed to TCDD and infected with influenza virus do not have an increased pulmonary virus burden suggests either that TCDD treatment alters the host response to infection, creating a cellular environment that is less supportive for viral growth, or that exposure to TCDD directly affects influenza virus, leading to impaired virus replication within lung epithelial cells.

Developmental Exposure to Bisphenol A Modulates Innate but Not Adaptive Immune Responses to Influenza A Virus Infection

“…Correlating with no change in the host’s ability to mount adaptive immunity against influenza virus infection, BPA exposure during development did not adversely affect host resistance to primary or recall infection. Based on these observation it appears that, in contrast to several other pollutants, such as dioxins and polychlorinated biphenyls, tobacco smoke, and lead [22], [23], [35], [49], [58]–[60], developmental exposure to BPA does not have significant influence on the magnitude or functional capacity of the antigen-specific adaptive component of the immune system.…”

“…The pulmonary viral burden was measured by determining the number of FFU present in lung homogenates [35]. Briefly, lungs were harvested from infected mice and mechanically homogenized.…”

Adverse effects of wood smoke PM2.5exposure on macrophage functions

“…dioxin). Numerous alterations in the immune system have been documented following TCDD exposure (Funatake et al, 2004; Ito et al, 2002; Kerkvliet et al, 2002; Lawrence et al, 2000; Matulka et al, 1997). Multiple types of PAHs and dioxin-like compounds have been described in WS (Ward et al, 2005; Ward & Lincoln 2006).…”

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

“…At maturity, female mice that were exposed developmentally (F1 generation offspring) or transgenerationally (F3 generation offspring) were infected with IAV. Nine days after infection, which is the peak day of this response (Lawrence et al., 2000, Lawrence et al., 2006), the percentage and number of CD8 + T cells in the lungs of TCDD lineage offspring were significantly reduced in F1 generation offspring, but not in the F3 generation (Table S1). The percentage of viral nucleoprotein (NP)-specific CD8 + T cells was reduced by about 60% in female mice that were developmentally exposed to TCDD (Figure 2A).…”