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Developmental exposure to bisphenol A modulates innate but not adaptive immune responses to influenza A virus infection.

Roy A, Bauer SM, Lawrence BP - PLoS ONE (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.

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.

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Developmental exposure to BPA does not alter primary disease outcomes from infection with influenza A virus.Developmentally exposed adult offspring were infected with influenza virus (HKx31). All mice were monitored for (A) body weight loss and (B) mortality for a period of at least 30 days post infection (n = 55/group). (C) To determine pulmonary viral burden, sub-groups of infected mice were sacrificed 3, 5, 7 or 10 days after infection and lungs were harvested (n≥5/group/time point). Viral FFU per lung per animal was determined by incubating lung homogenates on MDCK cells, as described in the Material and Methods section. The gray dotted line represents the limit of detection for the assay. Data represent mean ± SEM, and depict findings in female offspring. Parallel assessments were conducted in male adult offspring, and yielded similar results (data not shown).
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pone-0038448-g002: Developmental exposure to BPA does not alter primary disease outcomes from infection with influenza A virus.Developmentally exposed adult offspring were infected with influenza virus (HKx31). All mice were monitored for (A) body weight loss and (B) mortality for a period of at least 30 days post infection (n = 55/group). (C) To determine pulmonary viral burden, sub-groups of infected mice were sacrificed 3, 5, 7 or 10 days after infection and lungs were harvested (n≥5/group/time point). Viral FFU per lung per animal was determined by incubating lung homogenates on MDCK cells, as described in the Material and Methods section. The gray dotted line represents the limit of detection for the assay. Data represent mean ± SEM, and depict findings in female offspring. Parallel assessments were conducted in male adult offspring, and yielded similar results (data not shown).

Mentions: To examine the immunological competence of developmentally exposed adult offspring, we infected them with influenza virus (strain A/HKx31; H3N2) and examined a set of primary and secondary disease outcomes in female and male adult offspring. Primary outcomes included survival, changes in body weight as a measure of morbidity, and the amount of virus in the lung. Secondary outcomes included pulmonary inflammation, expression of key anti-viral genes, as well as virus-specific CD8+ T cell and antibody responses after primary and secondary infection. Following primary infection, we did not observe any differences in mortality, body weight change, or virus clearance from the lung, when we compared mice that were developmentally exposed to BPA to age- and sex-matched offspring of control-treated dams (Fig. 2). Given that influenza A virus strain HKx31 is generally considered to cause a relatively mild infection, we infected a separate group of developmentally exposed mice with a more lethal strain: influenza A virus CA/04/09 (H1N1). While this caused ≥ 50% mortality, we observed no difference in morbidity or mortality in the BPA- versus control-exposed groups (data not shown).


Developmental exposure to bisphenol A modulates innate but not adaptive immune responses to influenza A virus infection.

Roy A, Bauer SM, Lawrence BP - PLoS ONE (2012)

Developmental exposure to BPA does not alter primary disease outcomes from infection with influenza A virus.Developmentally exposed adult offspring were infected with influenza virus (HKx31). All mice were monitored for (A) body weight loss and (B) mortality for a period of at least 30 days post infection (n = 55/group). (C) To determine pulmonary viral burden, sub-groups of infected mice were sacrificed 3, 5, 7 or 10 days after infection and lungs were harvested (n≥5/group/time point). Viral FFU per lung per animal was determined by incubating lung homogenates on MDCK cells, as described in the Material and Methods section. The gray dotted line represents the limit of detection for the assay. Data represent mean ± SEM, and depict findings in female offspring. Parallel assessments were conducted in male adult offspring, and yielded similar results (data not shown).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3366985&req=5

pone-0038448-g002: Developmental exposure to BPA does not alter primary disease outcomes from infection with influenza A virus.Developmentally exposed adult offspring were infected with influenza virus (HKx31). All mice were monitored for (A) body weight loss and (B) mortality for a period of at least 30 days post infection (n = 55/group). (C) To determine pulmonary viral burden, sub-groups of infected mice were sacrificed 3, 5, 7 or 10 days after infection and lungs were harvested (n≥5/group/time point). Viral FFU per lung per animal was determined by incubating lung homogenates on MDCK cells, as described in the Material and Methods section. The gray dotted line represents the limit of detection for the assay. Data represent mean ± SEM, and depict findings in female offspring. Parallel assessments were conducted in male adult offspring, and yielded similar results (data not shown).
Mentions: To examine the immunological competence of developmentally exposed adult offspring, we infected them with influenza virus (strain A/HKx31; H3N2) and examined a set of primary and secondary disease outcomes in female and male adult offspring. Primary outcomes included survival, changes in body weight as a measure of morbidity, and the amount of virus in the lung. Secondary outcomes included pulmonary inflammation, expression of key anti-viral genes, as well as virus-specific CD8+ T cell and antibody responses after primary and secondary infection. Following primary infection, we did not observe any differences in mortality, body weight change, or virus clearance from the lung, when we compared mice that were developmentally exposed to BPA to age- and sex-matched offspring of control-treated dams (Fig. 2). Given that influenza A virus strain HKx31 is generally considered to cause a relatively mild infection, we infected a separate group of developmentally exposed mice with a more lethal strain: influenza A virus CA/04/09 (H1N1). While this caused ≥ 50% mortality, we observed no difference in morbidity or mortality in the BPA- versus control-exposed groups (data not shown).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.

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.

Show MeSH
Related in: MedlinePlus