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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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Maternal BPA exposure alters the tissue pathology following influenza A virus infection.Adult offspring of treated dams were infected with influenza virus (HKx31). To examine lung pathology, sub-groups of infected mice were sacrificed 3, 7 or 10 days following infection and lungs were fixed in-situ with 10% neutral buffered saline. Paraffin embedded tissues were cut in 5 µM think sections and stained with H&E. (A) Representative images of tissue sections from infected female mice are depicted. All images are at the same magnification. (B) Tissue sections from all mice in each group were scored based on the degree of inflammatory cell accumulation, as outlined in the Material and Methods section. Data in the graphs represent mean ± SEM (n = 5/group/time point); *p≤0.05.
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pone-0038448-g003: Maternal BPA exposure alters the tissue pathology following influenza A virus infection.Adult offspring of treated dams were infected with influenza virus (HKx31). To examine lung pathology, sub-groups of infected mice were sacrificed 3, 7 or 10 days following infection and lungs were fixed in-situ with 10% neutral buffered saline. Paraffin embedded tissues were cut in 5 µM think sections and stained with H&E. (A) Representative images of tissue sections from infected female mice are depicted. All images are at the same magnification. (B) Tissue sections from all mice in each group were scored based on the degree of inflammatory cell accumulation, as outlined in the Material and Methods section. Data in the graphs represent mean ± SEM (n = 5/group/time point); *p≤0.05.

Mentions: The equivalent capacity for virus clearance suggested that developmental exposure might not overtly compromise aspects of immune function crucial for surviving infection. This idea is relevant because the global burden associated with influenza virus stems less from mortality and more from the impact of infection-related illness, resulting co-morbidities, and lost productivity. Two aspects of the host immune response that often influence the degree of illness are pulmonary inflammation and mediators of anti-viral immunity [41], [42]. Thus, to further evaluate whether developmental exposure to BPA could have subtle effects on the immune system, we examined pulmonary inflammation and cytokine/chemokine gene expression levels in infected lung tissues. We compared lung inflammation in mice developmentally exposed to vehicle or BPA at three critical times following influenza A virus infection: 1) during the peak of virus replication in the lung (day 3 post-infection [p.i.]), 2) during early virus clearance phase (day 7 p.i.), and 3) during the peak of CD8+ T cell mediated response, which ultimately clears virus from the lung and generally dictates the overall outcome of the disease (day 10 p.i.). As shown in Fig. 3, mice that were developmentally exposed to BPA or vehicle control exhibited a similar degree of bronchopulmonary inflammation the early stages of infection. However, there was significantly less severe pulmonary inflammation 7 days after infection. By day 10 p.i., the extent of inflammation returns to an equivalent level in both groups of mice.


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)

Maternal BPA exposure alters the tissue pathology following influenza A virus infection.Adult offspring of treated dams were infected with influenza virus (HKx31). To examine lung pathology, sub-groups of infected mice were sacrificed 3, 7 or 10 days following infection and lungs were fixed in-situ with 10% neutral buffered saline. Paraffin embedded tissues were cut in 5 µM think sections and stained with H&E. (A) Representative images of tissue sections from infected female mice are depicted. All images are at the same magnification. (B) Tissue sections from all mice in each group were scored based on the degree of inflammatory cell accumulation, as outlined in the Material and Methods section. Data in the graphs represent mean ± SEM (n = 5/group/time point); *p≤0.05.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0038448-g003: Maternal BPA exposure alters the tissue pathology following influenza A virus infection.Adult offspring of treated dams were infected with influenza virus (HKx31). To examine lung pathology, sub-groups of infected mice were sacrificed 3, 7 or 10 days following infection and lungs were fixed in-situ with 10% neutral buffered saline. Paraffin embedded tissues were cut in 5 µM think sections and stained with H&E. (A) Representative images of tissue sections from infected female mice are depicted. All images are at the same magnification. (B) Tissue sections from all mice in each group were scored based on the degree of inflammatory cell accumulation, as outlined in the Material and Methods section. Data in the graphs represent mean ± SEM (n = 5/group/time point); *p≤0.05.
Mentions: The equivalent capacity for virus clearance suggested that developmental exposure might not overtly compromise aspects of immune function crucial for surviving infection. This idea is relevant because the global burden associated with influenza virus stems less from mortality and more from the impact of infection-related illness, resulting co-morbidities, and lost productivity. Two aspects of the host immune response that often influence the degree of illness are pulmonary inflammation and mediators of anti-viral immunity [41], [42]. Thus, to further evaluate whether developmental exposure to BPA could have subtle effects on the immune system, we examined pulmonary inflammation and cytokine/chemokine gene expression levels in infected lung tissues. We compared lung inflammation in mice developmentally exposed to vehicle or BPA at three critical times following influenza A virus infection: 1) during the peak of virus replication in the lung (day 3 post-infection [p.i.]), 2) during early virus clearance phase (day 7 p.i.), and 3) during the peak of CD8+ T cell mediated response, which ultimately clears virus from the lung and generally dictates the overall outcome of the disease (day 10 p.i.). As shown in Fig. 3, mice that were developmentally exposed to BPA or vehicle control exhibited a similar degree of bronchopulmonary inflammation the early stages of infection. However, there was significantly less severe pulmonary inflammation 7 days after infection. By day 10 p.i., the extent of inflammation returns to an equivalent level in both groups of mice.

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