Effects of binge alcohol exposure on Burkholderia thailandensis-alveolar macrophage interaction.

Abstract

Alcohol consumption has diverse and well-documented effects on the human immune system and its ability to defend against infective agents. One example is melioidosis, a disease caused by infection with Burkholderia pseudomallei, which is of public health importance in Southeast Asia and Northern Australia, with an expanding global distribution. While B.pseudomallei infections can occur in healthy humans, binge alcohol use is progressively being recognized as a major risk factor. Although binge alcohol consumption has been considered as a risk factor for the development of melioidosis, no experimental studies have investigated the outcomes of alcohol exposure on Burkholderia spp. infection. Therefore, we proposed the use of non-pathogenic B.thailandensis E264 as a useful BSL-1 model system to study the effects of binge alcohol exposure on bacteria and alveolar macrophage interactions. The MH-S alveolar macrophage (AMs) cell line was used to characterize innate immune responses to infection invitro. Our results showed that alcohol exposure significantly suppressed the uptake and killing of B.thailandensis by AMs. Alveolar macrophages incubated in alcohol (0.08%) for 3h prior to infection showed significantly lower bacterial uptake at 2 and 8h post infection. Activated AMs with IFN-γ and pre and post-incubation in alcohol when exposed to B.thailandensis released lower nitric oxide (NO) concentrations, compared to activated AMs with IFN-γ from non-alcoholic controls. As a result, B.thailandensis survival and replication increased ∼2.5-fold compared to controls. The presence of alcohol (1%) also increased bacterial survival within AMs. Alcohol significantly decreased bacterial motility compared to non-alcoholic controls. Increased biofilm formation was observed at 3 and 6h when bacteria were pre-incubated in (0.08%) alcohol. These results provide insights into binge alcohol consumption, a culturally prevalent risk factor, as a predisposing factor for melioidosis.