Mercury enhances susceptibility to murine leishmaniasis

The genetic background of mice infected with Leishmania major determines th e response to infection, resulting in a resistant or susceptible phenotype. Susceptible mice develop a T-helper type 2 (Th2)-type immune response foll owing infection distinguished by the development of interleukin (IL)-4 secr eting T cells in the lymph node and spleen. In SJL mice, which normally hea l L. major lesions, subtoxic doses of mercury induce an autoimmune syndrome characterized by an expansion of Th2 cells. In this study, we examined the effect of mercury administration on the outcome of L. major infection in S JL mice. We show that subtoxic doses of mercuric chloride (HgCl2) exacerbat e disease outcome in SJL mice resulting in increased footpad swelling and i ncreased parasite burdens. Furthermore, the effects of HgCl2 treatment on r esistance to L. major are time-dependent. The nonhealing phenotype was obse rved only if mice had been treated with HgCl2 prior to L. major infection f or at least 1 week, a timepoint at which mice treated with HgCl2 alone had increased splenocyte IL-4 production. HgCl2 treatment also increased produc tion of serum immunoglobulin (Ig)E and IgG1, two IL-4 dependent isotypes. T hese results show that HgCl2 treatment enhances the susceptibility to L. ma jor in SJL mice, consistent with the induction of host Th2 parameters. Thes e findings have implications for the role of mercury contamination in areas of endemic leishmaniasis.