A role for IgG immune complexes during infection with the intracellular pathogen Leishmania.
We examined the role of immunoglobulin (Ig)G antibodies in mediating host defense to the intracellular parasite, Leishmania. We show that IgG not only fails to provide protection against this intracellular pathogen, but it actually contributes to disease progression. The J(H) strain of BALB/c mice, which lack IgG because they have a targeted deletion in the Ig heavy chain (J) locus, were more resistant to infection with Leishmania major than were normal BALB/c mice. However, the passive administration of anti-Leishmania IgG caused J(H) mice to develop large lesions containing high numbers of parasites. Antibody administration correlated with an increase in interleukin (IL) 10 production in lesions, and blocking the murine IL-10 receptor prevented antibody-mediated disease exacerbation. In human patients with active visceral leishmaniasis, high IgG levels are predictive of disease. Patients with ongoing disease had high IgG antibody titers and no delayed-type hypersensitivity (DTH) responses to Leishmania antigens. This pattern was reversed upon disease resolution after treatment, resulting in a decrease in total IgG, which was accompanied by a progressive increase in DTH responsiveness. We conclude that IgG can cause a novel form of immune enhancement due to its ability to induce IL-10 production from macrophages.
Miles
Suzanne A
SA
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Conrad
Sean M
SM
Alves
Renata G
RG
Jeronimo
Selma M B
SM
Mosser
David M
DM
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D018320:Leishmania major / Q000276:immunology*; D007896:Leishmaniasis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000378:metabolism / Q000469:parasitology
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D016753:Interleukin-10