Trypanosoma cruzi, the causative agent of Chagas' disease, induces transient thymic aplasia early after infection-a phenomenon that stills lacks a molecular explanation. The parasite sheds an enzyme known as trans-sialidase (TS), which is able to direct transfer-sialyl residues among macromolecules. Because cell-surface sialylation is known to play a central role in the immune system, we tested whether the bloodstream-borne TS is responsible for the thymic alterations recorded during infection. We found that recombinant TS administered to naive mice was able to induce cell-count reduction mediated by apoptosis, mimicking cell subsets distribution and histologic findings observed during the acute phase of the infection. Thymocytes taken after TS treatment showed low response to Con A, although full ability to respond to IL-2 or IL-2 plus Con A was conserved, which resembles findings from infected animals. Alterations were found to revert several days after TS treatment. The administration of TS-neutralizing Abs to T. cruziinfected mice prevented thymus alterations. Results indicate that the primary target for the TS-induced apoptosis is the so-called ''nurse cell complex''. Therefore, we report here supporting evidence that TS is the virulence factor from T. cruzi responsible for the thymic alterations via apoptosis induction on the nurse cell complex, and that TS-neutralizing Abs elicitation during infection is associated with the reversion to thymic normal parameters.

Although a putative role has been attributed to inflammation in the pathogenesis of depressive disorders, the relationship of prostaglandins, known mediators of inflammation, and depression has not been elucidated. Clomipramine is an antidepressive drug with a pro-depressive paradoxical effect in adult rats when administrated neonatally. Using this effect as a model of depression, we investigated the differential expression of the cyclooxygenase (COX-2) gene in rat brains. Rats injected neonatally with clomipramine showed depressive-like symptoms in adulthood, as well as decreased levels of the brain-derived neurotrophic factor (BDNF) and a quantitative differential expression of the COX-2 gene (Real Time PCR) and protein (immunohistochemistry) in the hippocampus. As evidenced, the relationship between a key enzyme in the prostaglandin synthesis and biological and behavioral depression-like changes opens an interesting line of investigation regarding the molecular bases of depression and its potential treatment through immunomodulatory drugs.

Chagas' disease is a chronic, debilitating, multisystemic disorder that affects millions of people in Latin America. The protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas' disease, has a large number of O-glycosylated Thr/Ser/Pro-rich mucin molecules on its surface (TcMuc). These mucins are the main acceptors of sialic acid and have been suggested to play a role on various host-parasite interactions, such as adhesion to macrophages, protection from complement lysis, and immunomodulation of the immune response mounted by the host. To observe the immunologic effect obtained by the heterologous expression of a TcMuc gene in higher eukaryotic cells exposed to xenogeneic lymphocytes, we developed a strategy based on the transfection of a known T. cruzi mucin gene (TcMuc-e2) into Vero cells. In contrast to the brisk proliferation and activation of human lymphocytes observed at 3, 4, and 5 days induced by normal Vero cells, neither proliferation nor significant activation of human lymphocytes was observed with TcMuc-e2-transfected Vero cells. This TcMuc-e2 mucin-induced suppression of T cell response can be reversed by the addition of exogenous IL-2. In addition it was demonstrated that the immunosuppressive reaction was not related to the induction of an important degree of apoptosis in human lymphocytes. Posttranslational modification are required for the inhibitory effect that TcMuc-e2 exerts when transfected to Vero cells. O-glycosylation and sialylation are required to obtain the immunomodulatory effect as assessed by O-sialoglycoprotease and neuraminidase treatments. These results are consistent with other studies showing that surface glycoconjugates from T. cruzi and mammalian cells can induce an inhibition of the immune response.