title: Conservation of CD4+ T cell-dependent developmental mechanisms in the blood fluke pathogens of humans.
abstract: Schistosoma blood flukes are trematode parasites with a cosmopolitan distribution that infect over 200 million people globally. We previously showed that Schistosoma mansoni growth and development in the mammalian host is dependent on signals from host CD4+ T cells. To gain insight into the mechanisms that underlie this dependence, we sought to determine the evolutionary origins and limits of this aspect of the host-pathogen relationship. By infecting RAG-1-/- mice with a range of different schistosome species and strains, we tested several hypotheses concerning the time during Schistosoma evolution at which this dependence arose, and whether this dependence is specific to Schistosoma or is also found in other blood flukes. Our data indicate that the developmental dependence on CD4+ T cells previously described for S. mansoni is conserved in the evolutionarily basal species Schistosoma japonicum, suggesting this developmental adaptation arose early in Schistosoma evolution. We also demonstrate that the development of the more evolutionarily derived species Schistosoma haematobium and Schistosoma intercalatum are dependent on adaptive immune signals. Together, these data suggest that the blood fluke parasites of humans utilise common mechanisms to infect their hosts and to co-opt immune signals in the coordination of parasite development. Thus, exploitation of host-schistosome interactions to impair or prevent parasite development may represent a novel approach to combating all of the schistosome pathogens of humans.
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Erika W
authors.initials: EW
authors.lastname: Lamb
authors.forename: Emily T
authors.initials: ET
authors.lastname: Crow
authors.forename: K C
authors.initials: KC
authors.lastname: Lim
authors.forename: Yung-san
authors.initials: YS
authors.lastname: Liang
authors.forename: Fred A
authors.initials: FA
authors.lastname: Lewis
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Davies
mesh_terms: D000818:Animals; D005075:Biological Evolution; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D018398:Homeodomain Proteins / Q000502:physiology; D006790:Host-Parasite Interactions; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012547:Schistosoma / Q000145:classification / Q000254:growth & development* / Q000276:immunology; D012548:Schistosoma haematobium / Q000254:growth & development / Q000276:immunology; D012549:Schistosoma japonicum / Q000254:growth & development / Q000276:immunology; D012552:Schistosomiasis / Q000276:immunology* / Q000469:parasitology; D013045:Species Specificity
chemical_list: D018398:Homeodomain Proteins; C064658:RAG-1 protein