Immunopathology of Chagas disease - a historical overview.

Abstract

There are several factors which directly or in-directly contribute to lesions produced by infec-tion with Trypanosoma cruzi. Some of these fac-tors are inherent to the parasite (initial parasite-host interactions which are ligand-specific, pleo-morphism, tropism, virulence, genetic and anti-genic constitution, parasite number of the inocu-lum, reinfection, parasite strains, clonal selection,mixed populations, etc.); others are related to thehost (genetic constitution, sex, age, race, nutrition,immune response, professional macrophages andnon-permissible cells, muscle cells, peripheral andcentral neuroglia, fibroblasts, mast cells and oth-ers). As in other infectious diseases, in Chagas dis-ease, the mechanisms by which T. cruzi induceslesion are multi-faceted. Depending on thesemechanism anatomo-clinical forms will or will notappear. By whatever means T. cruzi infects its host,any cell of different tissues and organs can be ran-domly infected. Several molecules (80 to 200 kDa)responsible for cell adhesion and penetration havebeen identified on the surface of the parasite(Bosghetti et al. 1987, Alves 1996). After gainingaccess into the cell, the parasite multiplies and, atthis initial phase of the infection, are very aggres-sive since there is no immunity and no inflamma-tory reaction around parasitized cells. The escapefrom the parasitophorus vacuole into the host-cellis due to the action of a hemolysin which func-tions in acid pH. Thus, the host-cell bursts and bothepi and tripomastigote parasite forms as well asorganelles are released in the interstitium and workas an antigenic mosaic which will induce a rapid,parasite-specific and cell-mediated immune reac-tion. In consequence, an acute and focal inflam-matory reaction with the exudation of mononucle-ated cells appears around areas of necrosis. This isseen most notably as myocarditis, myositis (bothsmooth and striated muscles), periganglionitis,ganglionitis, perineuritis and neuritis. With the pro-gression of the immune response, parasite levelsin blood and tissues drop. Nevertheless, the para-site is not completely eliminated, even in the pres-ence of a Th1 lymphocyte response (IL-2 and IFNgamma) or circulating IgM and IgG antibodies.The mechanisms underlying the ability of theparasite to escape the immune response are verycomplex and not completely understood. Severalideas have been pursued to explain such phenom-enon, including the complexity and diversity ofreceptors needed for internalization, the escapefrom complement-mediated lysis, the endocytosisof antibodies by the parasite, the genetic polymor-phism, the expression of several antigenicimmunodeterminants at the same time, the anti-genic mimetism, the suppression of the release ofIFN gamma by Th1 lymphocytes, the polyclonalactivation of T and B cells and the excessive pro-duction of TNF α. Although T. cruzi can infectany cell type, there are strains with a greater tro-pism for certain cells, tissues and organs. Thus,the different anatomo-clinical presentations of thedisease will be determined by: (1) the tropism fordifferent organs; (2) the intensity of parasitism; (3)the intensity of the inflammatory response; (4) thebuild-up and evolution of the immune response.Depending on these factors, anatomo-clinicalforms, such as the cardiac or digestive forms, willdevelop into chronic fibrosing myocarditis withheart failure and/or in the megas, although tissueparasitism is almost absent. However a focal and/or diffuse inflammation is intense. Here, fibrosis(focal and diffuse fibrilopoesis) is the new obser-vation not noticed in the acute forms. In our view,tissue fibrosis associated with parasympatic den-ervation is the major cause for the progressive func-tional loss of the affected organ (Tafuri 1979).Although there is a vast literature about thesubject, there is little known about the intimateimmunological mechanisms which control thechanges in local and general reactivity of the or-ganisms during the evolution of the chagasic in-fection. For this reason, the reasons underlying thenatural history of Chagas disease is still not known.The focal acute inflammation evolves to an asymp-