Conservation of CD4+ T cell-dependent developmental mechanisms in the blood fluke pathogens of humans.
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.
Lamb
Erika W
EW
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Crow
Emily T
ET
Lim
K C
KC
Liang
Yung-san
YS
Lewis
Fred A
FA
Davies
Stephen J
SJ
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
D018398:Homeodomain Proteins; C064658:RAG-1 protein