title: The common gamma chain cytokines interleukin (IL)-2 and IL-7 indirectly modulate blood fluke development via effects on CD4+ T cells.
abstract: The human pathogen Schistosoma mansoni exhibits a highly evolved and intricate relationship with its host, evading immune destruction while co-opting CD4(+) T cell-driven mechanisms to facilitate parasite development and egg excretion. Because the common gamma ( gamma (c)) chain cytokine interleukin (IL)-7 is also implicated in modulating schistosome development, we investigated whether this effect is mediated indirectly through the essential role that IL-7 plays in CD4(+) T cell growth and survival. We demonstrate that attenuated schistosome development in the absence of IL-7 results from dysregulated T cell homeostasis and not from disruption of direct interactions between schistosomes and IL-7. We also identify an indirect role that another gamma (c) chain cytokine plays in schistosome development, demonstrating that IL-2 expression by CD4(+) T cells is essential for normal parasite development. Thus, cytokines critical for CD4(+) T cell survival and function can mediate indirect but potent effects on developing schistosomes and underscore the importance of CD4(+) T cells in facilitating schistosome development.
authors.affiliation: Tropical Disease Research Unit, Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Rebecca B
authors.initials: RB
authors.lastname: Blank
authors.forename: Erika W
authors.initials: EW
authors.lastname: Lamb
authors.forename: Anna S
authors.initials: AS
authors.lastname: Tocheva
authors.forename: Emily T
authors.initials: ET
authors.lastname: Crow
authors.forename: K C
authors.initials: KC
authors.lastname: Lim
authors.forename: James H
authors.initials: JH
authors.lastname: McKerrow
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Davies
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006706:Homeostasis; D007376:Interleukin-2 / Q000276:immunology*; D015851:Interleukin-7 / Q000276:immunology*; D008099:Liver / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis; D010270:Parasite Egg Count; D015375:Receptors, Interleukin-2 / Q000235:genetics; D020395:Receptors, Interleukin-7 / Q000235:genetics; D012550:Schistosoma mansoni / Q000254:growth & development* / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000469:parasitology*
chemical_list: D007376:Interleukin-2; D015851:Interleukin-7; D015375:Receptors, Interleukin-2; D020395:Receptors, Interleukin-7