Arsenic trioxide impairs primary human NK cell responses against influenza A virus

Abstract ID 20848 Poster Board 24 Arsenic is a naturally occurring contaminant that is commonly found in water supplies. Chronic exposure to arsenic has been associated with multisystem disease, including respiratory diseases such as viral infections. Arsenic is known to regulate immune cell activity and has been shown to alter NK cell frequency and function. However, our knowledge on effects of arsenic on NK cell response to influenza remains limited. The following study aims to identify the effects of arsenic trioxide on NK cell activation and function against influenza A virus in primary human immune cells . Primary human peripheral blood mononuclear cells were treated with environmentally-relevant concentrations of arsenic trioxide prior to an influenza A virus challenge. Flow cytometric analysis of NK cells showed arsenic trioxide significantly decreased NK cell viability. Additionally, NK cell activation markers, CD69 and NKp46, were reduced with increasing concentrations of arsenic. Consistently, the production of NK cell effector mediators, including IFNg, granzyme B and perforin, were significantly impaired with treatment of arsenic trioxide. Overall, these data suggest that environmentally relevant concentrations of arsenic trioxide impaired NK cell responses to influenza A virus, which could negatively impact NK cell-mediated host defense. Furthermore, this study suggests that coculture of primary human NK cells with virally-infected cells is a useful model that can be used to assess the impact of chemicals on the effector function of human NK cells. This study was supported by the NIH R01 ES024966 and R21 ES033830.