The Effect of Arsenic Exposure in an Adult Mouse Tuberculosis Model

Arsenic is a well-known human carcinogen, naturally forming in the earth’s crust and leaching into drinking water sources. However, there is growing evidence that arsenic may also affect the immune system, thereby manipulating the host’s response to infection. Specific to this study, there is epidemiological evidence of increased tuberculosis mortality rates following arsenic exposure in a unique study area in the North of Chile. The effect of arsenic on tuberculosis mortality risk appeared stronger in men compared to women. Here, we aim to verify this increase of tuberculosis burden post-arsenic exposure in an adult mouse model. Adult male C57Bl/6 and A/J mice (age 5 weeks) were chronically exposed to 0ppb, 100ppb or 1,000ppb inorganic arsenic, in the form of sodium (meta-)arsenite, in their drinking water. Three weeks after exposure started, mice were infected at 7-8 weeks of age to 100 or 10,000 colony forming units (CFU) of H37Rv strain of Mycobacterium tuberculosis (Mtb). CFU in lungs were assessed at 1, 7, and 28 days following infection to assess arsenic-induced differences in Mtb growth. Serum was also analyzed for select cytokine concentrations at these same time points and pre-infection. Our preliminary data indicates that arsenic may affect the innate and adaptive immune responses to Mtb infections, leading to higher Mtb burden in the lung at day 7 and 28 post-infection. In addition, we aim to investigate how arsenic specifically changes the function of macrophages, critical immune cells for controlling an Mtb infection. To this end, we analyzed nitric oxide, phagocytosis, and cytokine production of in vivo As-exposed macrophages. Our findings suggest a change in macrophage function that may alter overall host immune response to Mtb infection. 3 Future studies will focus on further investigating the causal mechanisms involved in the increased tuberculosis risk after arsenic exposur