Mercury enhances susceptibility to murine leishmaniasis.
The genetic background of mice infected with Leishmania major determines the response to infection, resulting in a resistant or susceptible phenotype. Susceptible mice develop a T-helper type 2 (Th2)-type immune response following infection distinguished by the development of interleukin (IL)-4 secreting T cells in the lymph node and spleen. In SJL mice, which normally heal 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 SJL mice. We show that subtoxic doses of mercuric chloride (HgCl2) exacerbate disease outcome in SJL mice resulting in increased footpad swelling and increased parasite burdens. Furthermore, the effects of HgCl2 treatment on resistance to L. major are time-dependent. The nonhealing phenotype was observed only if mice had been treated with HgCl2 prior to L. major infection for at least 1 week, a timepoint at which mice treated with HgCl2 alone had increased splenocyte IL-4 production. HgCl2 treatment also increased production of serum immunoglobulin (Ig)E and IgG1, two IL-4 dependent isotypes. These results show that HgCl2 treatment enhances the susceptibility to L. major in SJL mice, consistent with the induction of host Th2 parameters. These findings have implications for the role of mercury contamination in areas of endemic leishmaniasis.
Bagenstose
L M
LM
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Mentink-Kane
M M
MM
Brittingham
A
A
Mosser
D M
DM
Monestier
M
M
D000818:Animals; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis; D018320:Leishmania major / Q000276:immunology* / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D008627:Mercuric Chloride / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D018418:Th2 Cells / Q000276:immunology
D007074:Immunoglobulin G; D015847:Interleukin-4; D007073:Immunoglobulin E; D008627:Mercuric Chloride