The common γ chain cytokines interleukin (IL)-2 and IL-7 indirectly modulate blood fluke development via effects on CD4⁺ T cells

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 γ (γ_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 deregulated T cell homeostasis and not from disruption of direct interactions between schistosomes and IL-7. We also identify an indirect role that another γ_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.