A parent-of-origin effect determines the susceptibility of a non-informative F1 population to Trypanosoma cruzi infection in vivo

• Published in: PloS one Vol. 8; no. 2; p. e56347
• Main Authors: Silva, Grace K, Cunha, Larissa D, Horta, Catarina V, Silva, Alexandre L N, Gutierrez, Fredy R S, Silva, João S, Zamboni, Dario S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.02.2013; Public Library of Science (PLoS)
• Subjects: Agriculture; Animals; Biochemistry; Biology; Chagas disease; Chagas Disease - genetics; Development and progression; Disease Susceptibility; Female; Genes; Genetic aspects; Genetic engineering; Genetic Loci - genetics; Health aspects; Heredity; Histopathology; House mouse; Hybridization, Genetic; Identification; Immunology; In vivo methods and tests; Inbreeding; Infection; Infections; Infectious diseases; Lesions; Loci; Male; Medical research; Medical schools; Medicine; Mice; Organs; Parasitemia; Parasites; Pathogenesis; Phenotype; Plasmodium chabaudi; Protozoa; Rodents; Sex Characteristics; Species Specificity; Testosterone; Tropical diseases; Trypanosoma cruzi; Trypanosoma cruzi - physiology; Vector-borne diseases; Veterinary Science; Virulence (Microbiology); X Chromosome - genetics; Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0056347

The development of Chagas disease is determined by a complex interaction between the genetic traits of both the protozoan parasite, T. cruzi, and the infected host. This process is regulated by multiple genes that control different aspects of the host-parasite interaction. While determination of the relevant genes in humans is extremely difficult, it is feasible to use inbred mouse strains to determine the genes and loci responsible for host resistance to infection. In this study, we investigated the susceptibility of several inbred mouse strains to infection with the highly virulent Y strain of T. cruzi and found a considerable difference in susceptibility between A/J and C57BL/6 mice. We explored the differences between these two mouse strains and found that the A/J strain presented higher mortality, exacerbated and uncontrolled parasitemia and distinct histopathology in the target organs, which were associated with a higher parasite burden and more extensive tissue lesions. We then employed a genetic approach to assess the pattern of inheritance of the resistance phenotype in an F1 population and detected a strong parent-of-origin effect determining the susceptibility of the F1 male mice. This effect is unlikely to result from imprinted genes because the inheritance of this susceptibility was affected by the direction of the parental crossing. Collectively, our genetic approach of using the F1 population suggests that genes contained in the murine chromosome X contribute to the natural resistance against T. cruzi infection. Future linkage studies may reveal the locus and genes participating on the host resistance process reported herein.