Apoptotic lymphocytes treated with IgG from Trypanosoma cruzi infection increase TNF-alpha secretion and reduce parasite replication in macrophages.
Phagocytic removal of apoptotic lymphocytes exacerbates replication of Trypanosoma cruzi in macrophages. We investigated the presence of Ab against apoptotic lymphocytes in T. cruzi infection and the role of these Ab in parasite replication. Both control and chagasic serum contained IgG Ab that opsonized apoptotic lymphocytes. Treatment of apoptotic lymphocytes with purified IgG from chagasic, but not control serum, reduced T. cruzi replication in macrophages. The protective effect of chagasic IgG depended on Fcgamma receptors, as demonstrated by the requirement for the intact Fc portion of IgG, and the effect could be abrogated by treating macrophages with an anti-CD16/CD32 Fab fragment. Chagasic IgG displayed increased reactivity against a subset of apoptotic cell Ag, as measured by flow cytometry and immunoblot analyses. Apoptotic lymphocytes treated with chagasic IgG, but not control IgG, increased production of TNF-alpha, while decreasing production of TGF-beta1 by infected macrophages. Increased control of parasite replication required TNF-alpha production. Previous immunization with apoptotic cells or injection of apoptotic cells opsonized with chagasic IgG reduced parasitemia in infected mice. These results indicate that Ab raised against apoptotic cells could play a protective role in control of T. cruzi replication by macrophages.
Montalvão
Fabricio
F
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Almeida
Geisy M
GM
Silva
Elisabeth M
EM
Borges
Valeria M
VM
Vasconcellos
Rita
R
Takiya
Christina M
CM
Lopes
Marcela F
MF
Nunes
Marise P
MP
DosReis
George A
GA
D019264:Adoptive Transfer; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology* / Q000494:pharmacology; D017209:Apoptosis; D002478:Cells, Cultured; D014355:Chagas Disease / Q000276:immunology* / Q000469:parasitology / Q000628:therapy; D018920:Coculture Techniques; D005434:Flow Cytometry; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology / Q000628:therapy; D010587:Phagocytosis; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha