Initial induction of immunity, followed by suppression of responses to parasite antigens during Trypanosoma cruzi infection of mice

Abstract

Infection of a relatively resistant strain of mice (C57BL/6J) with the protozoan parasite Trypanosoma cruzi results in both the induction of parasite-specific T-helper cells and nonspecific suppressor cells. A time course study of the activation of help and suppression revealed that parasite-specific T-helper cell activity increases very early in infection (less than 12 days) at a time when suppression of non-parasite-specific responses and suppressor cell activity is increasing. Between 12 and 14 days of infection, the T-helper cell response to T. cruzi, as measured by the antibody response to hapten-T. cruzi in vitro, is suddenly and dramatically regulated. As reported previously, plastic and G-10 adherent cells appear to be responsible for the regulation of antibody responses to heterologous antigen during T. cruzi infection. These adherent suppressor cells are also responsible for the suppression of antibody responses to hapten-T. cruzi following the first 2 weeks of infection. Suppressor cells continue to regulate the parasite-specific response well into chronic infection even though the response to hapten-T. cruzi appears to return to normal levels. These results are the first to directly implicate nonspecific suppressor cells in the regulation of anti-T. cruzi humoral immune responses.

Gastric invasion by Trypanosoma cruzi and induction of protective mucosal immune responses

“…It is also possible that T. cruzi IMT can actively inhibit the secretion of inflammatory mediators such as IL-8 under conditions in which limited epithelial cell damage occurs as a result of only small numbers of developing pseudocysts. T. cruzi is well known to have immunosuppressive effects on the host (3,4,10,11,15,17,19,20,24,25,34,40,46,48,49,51), which may include anti-inflammatory effects. Future studies will need to address this issue.…”

“…Because the major forms of Chagas' disease are associated with chronic low-level intracellular infection which persists despite immunity that prevents overwhelming T. cruzi replication, a vaccine approach must focus on the complete prevention or eradication of persistent tissue parasitism. Once systemic T. cruzi infection occurs, the parasite is known to be capable of suppressing host immune responses (3,4,10,11,15,19,20,24,25,34,40,46,48,49,51). Therefore, the prevention of chronic infection may be the only achievable goal of vaccination.…”

CTLA‐4 regulates the murine immune response to Trypanosoma cruzi infection

“…Both the chronic stage and the acute illness, during which parasites circulate in the blood to spread to various tissues, are characterized by decreased T cell responsiveness both to polyclonal activators and to recall antigens (2,3). This immune suppression is believed to contribute to the pathogenicity of the parasite, and it has been subject of numerous studies because it manifests clearly in experimental models (4)(5)(6)(7)(8)(9).…”

Kinetics of Trypanosoma cruzi destruction in the mouse spleen

“…However, if macrophages are stimulated by sensitized T-cell lymphocyte soluble products, they become able to rapidly destroy internalized trypomastigotes 6 7 . These early events are crucial and may determined the outcome of the infection 14 . Suppressive chemotherapy accelerates this transitional phase and thus allows for a direct passage to the chronic stage, as has been demonstrated here and by others 3 .…”