Differential Regional Immune Response in Chagas Disease

Abstract

Following infection, lymphocytes expand exponentially and differentiate into effector cells to control infection and coordinate the multiple effector arms of the immune response. Soon after this expansion, the majority of antigen-specific lymphocytes die, thus keeping homeostasis, and a small pool of memory cells develops, providing long-term immunity to subsequent reinfection. The extent of infection and rate of pathogen clearance are thought to determine both the magnitude of cell expansion and the homeostatic contraction to a stable number of memory cells. This straight correlation between the kinetics of T cell response and the dynamics of lymphoid tissue cell numbers is a constant feature in acute infections yielded by pathogens that are cleared during the course of response. However, the regional dynamics of the immune response mounted against pathogens that are able to establish a persistent infection remain poorly understood. Herein we discuss the differential lymphocyte dynamics in distinct central and peripheral lymphoid organs following acute infection by Trypanosoma cruzi, the causative agent of Chagas disease. While the thymus and mesenteric lymph nodes undergo a severe atrophy with massive lymphocyte depletion, the spleen and subcutaneous lymph nodes expand due to T and B cell activation/proliferation. These events are regulated by cytokines, as well as parasite-derived moieties. In this regard, identifying the molecular mechanisms underlying regional lymphocyte dynamics secondary to T. cruzi infection may hopefully contribute to the design of novel immune intervention strategies to control pathology in this infection.

Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

“…The protective immunity to T. cruzi infection appears to depend on the CD4 ϩ and CD8 ϩ T cell expressions of gamma interferon (IFN-␥) (98,330). A central role played by CD8 ϩ T cells in the control of T. cruzi infection in mice was suggested during the acute and chronic stages, when antigen-independent immunodominant memory T cells reach persistently high levels (102,302). Regulatory CD4 ϩ CD25 ϩ T cells have a limited role in infection by T. cruzi (340).…”

“…The challenge of mice with immunogenic recombinant calreticulin induces an inflammatory reaction against a host 45-kDa protein. It was suggested that calreticulin-induced inflammatory infiltrates foster autoimmunity in Chagas' heart disease (102,324).…”

Trypanosoma cruzitrans-Sialidase Prevents Elicitation of Th1 Cell Response via Interleukin 10 and Downregulates Th1 Effector Cells

“…With an estimated total of 100 million people at risk of infection, about 8 to 10 million infected, and around 40,000 new cases per year, Chagas disease represents a major health, social, and economic problem in Latin America (1). The acute stage of infection is characterized by several transient abnormalities in the physiology of the immune system, leading to declines in cellular responses to mitogens, parasite antigens, or irrelevant antigens (2-4) that favor parasite colonization (5). These findings are consistent with reductions in the proliferation and expression of interleukin 2 (IL-2) and its high-affinity receptor IL-2R␣ (CD25) in murine T cells and human peripheral blood mononuclear cells (reviewed in reference 6).…”

Experiencia terapéutica en un centro para la enfermedad de Chagas

“…Así como en Chile no se dispone de BNZ, en diversos países no se usa NFX. Esto obedece a los efectos secundarios que ambos fármacos presentan y a diferencias de eficacia observadas, que probablemente están en relación a distintas cepas de Trypanosoma cruzi 20 . El NFX se ha demostrado más eficaz en Chile que en otros países de la región.…”