Protected Trypanosoma cruzi infection in rats born to mothers receiving interferon-gamma during gestation is associated with a decreased macrophage infectivity and preferential synthesis of specific IgG2b antibodies.

DIDOLI G; DÁVILA H; FELDMAN S; DI MASSO R; REVELLI S; BOTTASSO O; BOTTASSO OSCAR

INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY

Elsevier

Lugar: USA; Año: 2000 vol. 22 p. 45 - 55

0192-0561

We demonstrated that administration of interferon gamma (IFN-g) to pregnant rats conferred partial resistance in their o?spring to further challenge with Trypanosoma cruzi. Because of the e?ects of IFN-g on macrophage activation and immunoglobulin isotype selection, o?spring were now studied to ascertain whether this intervention modifies the in vitro replication of T. cruzi and nitric oxide (NO) production by peritoneal macrophages (PE), together with the anti-T. cruzi IgG isotypes. To evaluate the possibility of a detrimental e?ect of IFN-g, serum levels of anti-sulphatide autoantibodies were also investigated. O?spring were born to mothers undergoing one of the following procedures during gestation: treatment with recombinant rat IFN-g, 50,000 IU/rat, five times/week for3 weeks, which was started on the day of mating; infection with 106 trypomastigotes of T. cruzi at 7, 14, and 21 days after mating plus IFN-g treatment as given to the former group; the same protocol except that physiological saline was injected instead of IFN-g; injection of physiological saline only. O?spring were challenged at weaning with a similar dose of T. cruzi, to constitute four groups of infected young, plus an additional group of age-matcheduninfected rats born to control mothers. PE were harvested at day 7 postinfection (pi), exposed to parasites and further investigated for the replication of T. cruzi and NO production, whereas ELISA studies for measuring serum anti-T. cruzi IgG subclasses and anti-sulphatide autoantibodies were performed at day 30 pi. The number ofintracellular parasites in PE was markedly decreased in young born to IFN-g-treated mothers, this not being accompanied by higher nitrite levels in culture supernatants. O?spring delivered by IFN-g-treated mothers showed no higher serum concentrations of anti-sulphatide autoantibodies, but exhibited a preferential synthesis of anti-T.cruzi IgG2b antibodies. This rat isotype is known to fix complement and constitutes the rat counterpart of IgG2a mouse immunoglobulins whose synthesis is favoured by IFN-g.