The determinants of Chagas disease: connecting parasite and host genetics.
As a consequence of infection by Trypanosoma cruzi, 30% of victims may develop chronic Chagas disease, which presents a spectrum of pathology including cardiomyopathy, megacolon and megaesophagus. The outcome of infection in a particular individual is the result of a set of complex interactions among the host genetic background, environmental and social factors, and the genetic composition of the parasite, all of which can be complicated by mixed infections and re-infections. Initially we consider what is known about the genetic structure and biological properties of the protozoan. Currently, six distinct subgroups have been characterized by different combinations of four distinct genotypic classes. The recent demonstration of genetic exchange via non-meiotic cell fusion illustrates a mechanism by which maintained heterogeneous polyploidy may have been generated in these parasites. Subsequently, we consider factors in humans and in experimental mouse-infection and tissue culture models that have contributed to our understanding of the host's susceptibility or resistance to disease. Identification of the direct players in host-pathogen interactions at the establishment and chronic phases of the disease is perhaps the best hope of a clinical handle for treatment. At some point in the future, these disparate areas of study will have to come together. It is to be hoped that this scientific fusion will result in better prognosis and treatment of Chagas disease.
Campbell
David A
DA
Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095-1489, USA. dc@ucla.edu
Westenberger
Scott J
SJ
Sturm
Nancy R
NR
D000818:Animals; D000941:Antigens / Q000737:chemistry; D015415:Biomarkers; D014355:Chagas Disease / Q000235:genetics* / Q000469:parasitology* / Q000473:pathology; D004195:Disease Models, Animal; D005544:Forecasting; D014644:Genetic Variation; D006790:Host-Parasite Interactions; D006801:Humans; D051379:Mice; D010271:Parasites / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D011123:Polyploidy; D014349:Trypanosoma cruzi / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*
D000941:Antigens; D015415:Biomarkers