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Low-dose arsenic compromises the immune response to influenza A infection in vivo.

Kozul CD, Ely KH, Enelow RI, Hamilton JW - Environ. Health Perspect. (2009)

Bottom Line: Arsenic was associated with a number of significant changes in response to influenza, including an increase in morbidity and higher pulmonary influenza virus titers on day 7 post-infection.We also found many alterations in the immune response relative to As-unexposed controls, including a decrease in the number of dendritic cells in the mediastinal lymph nodes early in the course of infection.Alterations in response to repeated lung infection may also contribute to other chronic illnesses, such as bronchiectasis, which is elevated by As exposure in epidemiology studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire, USA.

ABSTRACT

Background: Arsenic exposure is a significant worldwide environmental health concern. We recently reported that 5-week exposure to environmentally relevant levels (10 and 100 ppb) of As in drinking water significantly altered components of the innate immune response in mouse lung, which we hypothesize is an important contributor to the increased risk of lung disease in exposed human populations.

Objectives: We investigated the effects of As exposure on respiratory influenza A (H1N1) virus infection, a common and potentially fatal disease.

Methods: In this study, we exposed C57BL/6J mice to 100 ppb As in drinking water for 5 weeks, followed by intranasal inoculation with a sub lethal dose of influenza A/PuertoRico/8/34 (H1N1) virus. Multiple end points were assessed postinfection.

Results: Arsenic was associated with a number of significant changes in response to influenza, including an increase in morbidity and higher pulmonary influenza virus titers on day 7 post-infection. We also found many alterations in the immune response relative to As-unexposed controls, including a decrease in the number of dendritic cells in the mediastinal lymph nodes early in the course of infection.

Conclusions: Our data indicate that chronic As exposure significantly compromises the immune response to infection. Alterations in response to repeated lung infection may also contribute to other chronic illnesses, such as bronchiectasis, which is elevated by As exposure in epidemiology studies.

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Alteration in cell numbers at day 0, 36 hr, day 3, and day 7 p.i. in BALF of mice exposed to control water or water containing 100 ppb As (Flu + As) followed by inoculation with influenza A. (A) Number of viable nucleated cells recovered from BALF. (B, C) Extrapolation of the total number of macrophages (B) and neutrophils (C) recovered from BALF. See “Materials and Methods” for experimental details. For A–C, data represent mean ± SEM from one representative experiment (n = 5–6 per group). (D) Neutrophils, macro phages (Macs), and lymphocytes shown as percentages of the total cells recovered.*p < 0.05, **p < 0.01, and #p < 0.001 determined by two-tailed Student’s t-test.
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f4-ehp-117-1441: Alteration in cell numbers at day 0, 36 hr, day 3, and day 7 p.i. in BALF of mice exposed to control water or water containing 100 ppb As (Flu + As) followed by inoculation with influenza A. (A) Number of viable nucleated cells recovered from BALF. (B, C) Extrapolation of the total number of macrophages (B) and neutrophils (C) recovered from BALF. See “Materials and Methods” for experimental details. For A–C, data represent mean ± SEM from one representative experiment (n = 5–6 per group). (D) Neutrophils, macro phages (Macs), and lymphocytes shown as percentages of the total cells recovered.*p < 0.05, **p < 0.01, and #p < 0.001 determined by two-tailed Student’s t-test.

Mentions: We investigated cellular infiltration into the lungs at 36 hr and at day 3 and day 7 p.i. We previously reported that exposure to 100 ppb As for 5 weeks in uninfected mice did not induce changes in the total number of cells recovered from BALF, nor did it alter gross changes in lung histology (Andrew et al. 2007; Kozul et al. 2009). However, in the present experimental model, we observed significant differences in the total number of cells recovered postinfection from the BALF of control and As-exposed mice. At 36 hr and day 3 p.i., As-exposed mice had a significant decrease in the total number of cells recovered from the BALF compared with control mice. Conversely, at day 7 p.i., As-exposed mice had a significant increase in the number of cells in BALF (Figure 4A) relative to controls.


Low-dose arsenic compromises the immune response to influenza A infection in vivo.

Kozul CD, Ely KH, Enelow RI, Hamilton JW - Environ. Health Perspect. (2009)

Alteration in cell numbers at day 0, 36 hr, day 3, and day 7 p.i. in BALF of mice exposed to control water or water containing 100 ppb As (Flu + As) followed by inoculation with influenza A. (A) Number of viable nucleated cells recovered from BALF. (B, C) Extrapolation of the total number of macrophages (B) and neutrophils (C) recovered from BALF. See “Materials and Methods” for experimental details. For A–C, data represent mean ± SEM from one representative experiment (n = 5–6 per group). (D) Neutrophils, macro phages (Macs), and lymphocytes shown as percentages of the total cells recovered.*p < 0.05, **p < 0.01, and #p < 0.001 determined by two-tailed Student’s t-test.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2737023&req=5

f4-ehp-117-1441: Alteration in cell numbers at day 0, 36 hr, day 3, and day 7 p.i. in BALF of mice exposed to control water or water containing 100 ppb As (Flu + As) followed by inoculation with influenza A. (A) Number of viable nucleated cells recovered from BALF. (B, C) Extrapolation of the total number of macrophages (B) and neutrophils (C) recovered from BALF. See “Materials and Methods” for experimental details. For A–C, data represent mean ± SEM from one representative experiment (n = 5–6 per group). (D) Neutrophils, macro phages (Macs), and lymphocytes shown as percentages of the total cells recovered.*p < 0.05, **p < 0.01, and #p < 0.001 determined by two-tailed Student’s t-test.
Mentions: We investigated cellular infiltration into the lungs at 36 hr and at day 3 and day 7 p.i. We previously reported that exposure to 100 ppb As for 5 weeks in uninfected mice did not induce changes in the total number of cells recovered from BALF, nor did it alter gross changes in lung histology (Andrew et al. 2007; Kozul et al. 2009). However, in the present experimental model, we observed significant differences in the total number of cells recovered postinfection from the BALF of control and As-exposed mice. At 36 hr and day 3 p.i., As-exposed mice had a significant decrease in the total number of cells recovered from the BALF compared with control mice. Conversely, at day 7 p.i., As-exposed mice had a significant increase in the number of cells in BALF (Figure 4A) relative to controls.

Bottom Line: Arsenic was associated with a number of significant changes in response to influenza, including an increase in morbidity and higher pulmonary influenza virus titers on day 7 post-infection.We also found many alterations in the immune response relative to As-unexposed controls, including a decrease in the number of dendritic cells in the mediastinal lymph nodes early in the course of infection.Alterations in response to repeated lung infection may also contribute to other chronic illnesses, such as bronchiectasis, which is elevated by As exposure in epidemiology studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire, USA.

ABSTRACT

Background: Arsenic exposure is a significant worldwide environmental health concern. We recently reported that 5-week exposure to environmentally relevant levels (10 and 100 ppb) of As in drinking water significantly altered components of the innate immune response in mouse lung, which we hypothesize is an important contributor to the increased risk of lung disease in exposed human populations.

Objectives: We investigated the effects of As exposure on respiratory influenza A (H1N1) virus infection, a common and potentially fatal disease.

Methods: In this study, we exposed C57BL/6J mice to 100 ppb As in drinking water for 5 weeks, followed by intranasal inoculation with a sub lethal dose of influenza A/PuertoRico/8/34 (H1N1) virus. Multiple end points were assessed postinfection.

Results: Arsenic was associated with a number of significant changes in response to influenza, including an increase in morbidity and higher pulmonary influenza virus titers on day 7 post-infection. We also found many alterations in the immune response relative to As-unexposed controls, including a decrease in the number of dendritic cells in the mediastinal lymph nodes early in the course of infection.

Conclusions: Our data indicate that chronic As exposure significantly compromises the immune response to infection. Alterations in response to repeated lung infection may also contribute to other chronic illnesses, such as bronchiectasis, which is elevated by As exposure in epidemiology studies.

Show MeSH
Related in: MedlinePlus