Group 2 Innate Lymphoid Cell Proportions Are Diminished in Young Helminth Infected Children and Restored by Curative Anti-helminthic Treatment

Abstract

Group 2 Innate lymphoid cells (ILC2s) are innate cells that produce the TH2 cytokines IL-5 and IL-13. The importance of these cells has recently been demonstrated in experimental models of parasitic diseases but there is a paucity of data on ILC2s in the context of human parasitic infections and in particular of the blood dwelling parasite Schistosoma haematobium. In this case-control study human peripheral blood ILC2s were analysed in relation to infection with the helminth parasite Schistosoma haematobium. Peripheral blood mononuclear cells of 36 S. haematobium infected and 36 age and sex matched uninfected children were analysed for frequencies of ILC2s identified as Lin-CD45+CD127+CD294+CD161+. ILC2s were significantly lower particularly in infected children aged 6–9 years compared to healthy participants. Curative anti-helminthic treatment resulted in an increase in levels of the activating factor TSLP and restoration of ILC2 levels. This study demonstrates that ILC2s are diminished in young helminth infected children and restored by removal of the parasites by treatment, indicating a previously undescribed association between a human parasitic infection and ILC2s and suggesting a role of ILC2s before the establishment of protective acquired immunity in human schistosomiasis. Understanding how immune responses are generated is critical for vaccine development. There are comparatively few studies on the interface between the innate and adaptive immune system in generating protective immune responses. Infections with helminth parasites, a cause of neglected tropical diseases, have a huge collective impact on public health in affected developing countries. Helminths are associated with a complex type 2 immune response mediated by cytokines characteristically produced by adaptive T helper 2 cells (T_H2). However in recent years a newly described type of innate immune cells has been shown to produce T_H2 cytokines. This cell type was subsequently called ‘Group 2 innate lymphoid cells’ (ILC2s). The importance of these cells has been demonstrated in experimental models of helminth infection as well as in allergic diseases. The present study describes changes in human ILC2s during the human helminth infection schistosomiasisas (bilharzia). Our study shows that the proportions of ILC2s, were lower in young, but not older infected children when compared to uninfected participants, suggesting a role for ILC2s before the establishment of helminth protective acquired immunity. Furthermore ILC2s were restored after curative treatment of the helminth infection. Human mechanistic studies will determine if the association between ILC2s and schistosome infection is causal or a marker of resistance to infection.