Intracellular survival of Staphylococcus aureus due to alteration of cellular activity in arsenic and lead intoxicated mature Swiss albino mice

The role of heavy metals like arsenic (As) and lead (Pb) as environmental toxicants is established. However, the exact mechanism of their effect on immunocompetent cell activity is not well known. Staphylococcus aureus is a virulent pathogen that has the ability to cause a variety of potentially life-threatening infections. The objective of our study was to demonstrate in an experimental mouse model of bacteremic S. aureus infection, bacterial clearance from blood and spleen in arsenic, lead treated and control group of mice. Bacterial density was measured in blood and spleen after 0, 24, 48 and 72 h post-infection. Our findings show a significant increase in bacterial load in blood (P<0.025 for arsenic and P<0.01 for lead) and delayed bacterial clearance by spleen in both arsenic (P<0.05) and lead (P<0.025) treated groups as compared to control, thus highlighting an immuno-compromised state following heavy metal exposure. To further elucidate immunomodulatory effects of both arsenic and lead, cell function studies were performed on splenic macrophages (M(phi)) isolated from lead and arsenic treated as well as control group of mice. Our findings show a decrease in cell adhesion property (P<0.005) of splenic M(phi)s from 2.9925+/-0.053 in control to 1.395+/-0.106 in arsenic and 0.8835+/-0.0106 in lead treated mice at 60 min. Morphologic alteration of the splenic M(phi)s showed an increase (As: P<0.05, Pb: P<0.0005) in both arsenic (6.876+/-0.3287%) and lead (16.55+/-1.051%) treated mice to control (2.649+/-1.238%) which may be responsible for the formers' reduced functional status. The chemotactic index, a measure of chemotactic migration of the macrophages toward immune serum, was 16.43+/-1.007 in control cell and was reduced (P<0.0005) to 4.19+/-0.393 in arsenic and 2.92+/-0.649 in lead treated mice at 60 min. These altered cell functions could probably explain the intracellular survival of S. aureus but such a causal relationship awaits further detailed examination.