Low-Dose Arsenic Compromises the Immune Response to Influenza A Infection in Vivo

Abstract

BackgroundArsenic 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.ObjectivesWe investigated the effects of As exposure on respiratory influenza A (H1N1) virus infection, a common and potentially fatal disease.MethodsIn 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.ResultsArsenic 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.ConclusionsOur 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.

Determination of environmentally relevant exposure concentrations of polybrominated diphenyl ethers for in vitro toxicological studies

“…Although it is not a new concept, the study of environmentally relevant doses (concentrations) has been the focus of recent attention (Bardullas et al, 2009;Kozul et al, 2009). Myers et al (2009) concluded that high dose experiments could not be used to predict low dose results.…”

Inorganic arsenic in Chinese food and its cancer risk

“…Whereas a strong dose-response relationship between As in tubewell water and skin lesion development, a precursor of skin cancer, has been observed, with even low exposure to As was shown to be problematic (Ahsan et al, 2006). Low level As intake may also play a role in diabetes prevalence, based on findings from a crosssectional study of 788 adults in the USA (Navas-Acien et al, 2008), in addition to impairing H1N1 infection immune system in responses (Kozul et al, 2009). These research findings amongst others have prompted critical re-evaluation of exposure thresholds for As (WHO/ FAO, 2010).…”

Arsenic Handicap? Prenatal Exposure Worsens Influenza Infections in Young Mice

“…1 Arsenic exposure has also been associated with altered gene expression in lung tissue from mice, including reduced expression of genes involved in innate immune responses. 2 But it's still unclear how arsenic might modify acute inflammatory responses during early-life infections and the subsequent effects on lung structure and function.…”

“…However, the EPA standard does not cover private wells; by one estimate, as many as 25 million people in the United States who obtain their drinking water from private wells may be exposed to arsenic levels above the EPA standard. 1 Stanton suggests repeating the mouse experiments with 10 ppb inorganic arsenic to see if the influenza response still worsens. Given current guidance on arsenic in drinking water and apple juice, "We'd want to know that," says Stanton.…”