Chagas' disease: an update on immune mechanisms and therapeutic strategies

Abstract

* Introduction * Chagas' disease * Chemotherapy * Immune response in experimental T. cruzi infection * Immune response in human beings infected with T. cruzi * Immune response in the treatment of chagasic infection * The need for new therapeutic alternatives for Chagas' disease * Conclusions The final decade of the 20th century was marked by an alarming resurgence in infectious diseases caused by tropical parasites belonging to the kinetoplastid protozoan order. Among the pathogenic trypanosomatids, some species are of particular interest due to their medical importance. These species include the agent responsible for Chagas' disease, Trypanosoma cruzi. Approximately 8 to 10 million people are infected in the Americas, and approximately 40 million are at risk. In the present review, we discuss in detail the immune mechanisms elicited during infection by T. cruzi and the effects of chemotherapy in controlling parasite proliferation and on the host immune system.

Fig 1

Schematic representation of the Trypanosoma cruzi life cycle. Replicative, non-infective epimastigote forms (A), predominantly present in the insect vector, give rise to non-replicative, infective metacyclic trypomastigotes (B). Metacyclic forms must invade the host cells and differentiate into replicative amastigote forms (C) to establish the infection. These forms give rise to a transient stage called intracellular epimastigotes (D), which subsequently differentiate into trypomastigotes (E). Trypomastigotes can disseminate in the mammalian host through the bloodstream. The insect vector eventually can take these forms during its bloodmeal. The cycle ends when the ingested trypomastigotes differentiate again into epimastigotes (A), which colonize the digestive tube of a new insect.

Fig 2

Molecular formula of BZL and NF.

Fig 3

Schematic representation of the protective immune response during T. cruzi acute infection. Antigen-presenting cells are among the first cells that become infected by the trypomastigotes when they enter the mammalian host. Normally, the cells react by up-regulating IL-6, IL-1β, TNF-α, IL-12 and nitric oxide in an attempt to control the infection. NK cells are among the first line of responders and usually produce high levels of IFN-γ when stimulated by IL-12. The stimulus of the Th1 profile and the CD8⁺ T cells contributes to eliminate the intracellular amastigotes in infected tissues. On the other hand, the parasite antigens stimulate a Th2 profile which contributes to the production of specific antibodies.