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

Abstract

Bisphenol A (BPA) is used in numerous products, such as plastic bottles and food containers, from which it frequently leaches out and is consumed by humans. There is a growing public concern that BPA exposure may pose a significant threat to human health. Moreover, due to the widespread and constant nature of BPA exposure, not only adults but fetuses and neonates are also exposed to BPA. There is mounting evidence that developmental exposures to chemicals from our environment, including BPA, contribute to diseases late in life; yet, studies of how early life exposures specifically alter the immune system are limited. Herein we report an examination of how maternal exposure to a low, environmentally relevant dose of BPA affects the immune response to infection with influenza A virus. We exposed female mice during pregnancy and through lactation to the oral reference dose for BPA listed by the US Environmental Protection Agency, and comprehensively examined immune parameters directly linked to disease outcomes in adult offspring following infection with influenza A virus. We found that developmental exposure to BPA did not compromise disease-specific adaptive immunity against virus infection, or reduce the host’s ability to clear the virus from the infected lung. However, maternal exposure to BPA transiently reduced the extent of infection-associated pulmonary inflammation and anti-viral gene expression in lung tissue. From these observations, we conclude that maternal exposure to BPA slightly modulates innate immunity in adult offspring, but does not impair the anti-viral adaptive immune response, which is critical for virus clearance and survival following influenza virus infection.

Prenatal exposure to bisphenol-A is associated with Toll-like receptor–induced cytokine suppression in neonates

“…In contrast, studies that implied inhibitory effect of BPA on cytokine production had experimental settings that pretreated immune cells with BPA followed by infection (bacteria or virus) or stimulation with lipopolysaccharide. The reduction in cytokine production could be explained by reduced neutrophils activity or downregulation of nitric oxide production caused by BPA exposure, thus leading to inappropriate immune response to defend against invading pathogens (15,22,23). In agreement with the later results, we had shown prenatal BPA exposure to reduce TNF-α response to TLR3 and 4 stimulation, and IL-6 response to TLR7-8 in the neonatal mononuclear cell.…”

“…Second, several reports have shown cytokine production to respond to BPA in a dose-dependent manner (15,20,21,23). In some studies in which lower doses of BPA were used, no effect was seen on ex vivo immune cell function or disease progression in vivo (22,28,29). Thus, it is possible that the extent of cytokine suppression exposed to low and environmentally relevant BPA level, such as in our study, was not sufficient to significantly increase the risk of infection or nasopharyngeal bacterial colonization in infants.…”

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

“…[3][4][5]19,[45][46][47] In animal and in vitro models BPA has been observed to increase the production of the proallergic cytokine IL-4 and serum IgE and to promote eosinophilic inflammation in the airways. 4,45 Results of a study with mice also suggest that prenatal BPA can affect the innate immune system but not the antiviral adaptive immune response.…”

Low dose effects of bisphenol A

“…[141][142][143][144][145] These studies typically show effects of BPA on some aspects of immune response, but not all (i.e., altered innate but not adaptive immune responses, effects in some organs but not others, etc.). Because these studies used different agents to invoke immune responses and assessed different organs' responses, there is not yet enough evidence to determine whether the effects of BPA on the immune system are consistent.…”