Pathogenesis and Modulation of Immune Function - Chagas’ Disease

Pathogenesis and Modulation of Immune Function

PATHOGENESIS

The pathogenesis of acute Chagas’ disease is not in dispute. On standard histo-pathological study, inflammatory lesions are found to co-localize with abundant parasites, demonstrating that inflammatory damage is directed to the parasite. The pathophysiology of chronic Chagas’ disease is still in question, but the compet-ing (nonexclusive) views are that disease results from an autoimmune response directed at the affected organ systems or from damage resulting from inflammation related to the persistence of the parasite. Supporting the autoimmune hypothesis are observations that live T. cruzipara-sites have been difficult to demonstrate in involved organs by conventional histologi-cal study and that autoimmune T cells and antibodies develop during infection with T. cruzi. Furthermore, autoimmune anti-bodies and autoimmune T cells have been associated with chronic Chagas’ disease or lesions. Some T. cruzi antigens molecularly mimic affected host tissues. It is hypothe-sized that the chronic infection leads to loss of tolerance and, combined with antigenic mimicry, results in specific autoimmune attack of cardiac, gut, and peripheral ner-vous tissues.

The other hypothesis is that progres-sive inflammation directed at parasites that reside in target organs cause the pathologic damage of chronic infection. Studies that support this hypothesis have found that parasite antigens and DNA can be detected in many chronic inflammatory infiltrate and that parasitologic treatment of chronically infected animals or humans tends to lead to improvement and resolu-tion of disease. The evidence for the com-peting theories of chronic Chagas’ disease pathogenesis is discussed in detail in the next section. Since the autoimmune and parasite-directed pathogenesis theories are not mutually exclusive and since evi-dence exists to support each of them, it seems likely that both mechanisms could be pathogeneic in chronic Chagas’ disease.