Alterations in murine macrophage reactivity and bactericidal efficacy following exposure to an environmentally relevant mixture of organochlorine pesticide compounds

Abstract

While there are a number of factors which may promote chronic inflammation, a major factor is pro-inflammatory activation of resident and infiltrating macrophages. Recently, exposures to persistent organic pollutants including organochlorine (OC) pesticides have been implicated in dysregulation of macrophage function. However, the majority of these studies examined single compound effects and not mixture-based effects. To this end, the present study investigated the effects of an environmentally relevant mixture of three prevalent OC pesticide compounds on macrophage function. Briefly, J77A.1 macrophages were exposed to a mixture of dichlorodiphenyldichloroethylene, trans-nonachlor, and oxychlordane (DTO; 0.2–20 μM) for 24 h then effects on cell viability, caspase 3/7 activity, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), antibacterial activity, and pro-inflammatory cytokine production were determined. Exposure to DTO significantly increased caspase activity and ROS production. The highest concentration of DTO significantly increased Staphylococcus aureus uptake while decreasing phagolysosome formation and bactericidal efficacy. Lastly, exposure to DTO significantly increased basal production of Mcp-1. Taken together, the present study demonstrates an environmentally relevant mixture of OC pesticide compounds increases macrophage ROS and Mcp-1 production while decreasing macrophage bactericidal efficacy which may adversely affect macrophage function and increase susceptibility to S. aureus infection.