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

Abstract

BackgroundGroup 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.Methodology/Principal FindingsIn 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.ConclusionThis 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.

Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis

“…It has been reported that the abundance of ILC2s is diminished in young children infected with Schistosoma haematobium and that anti-worm treatment restores ILC2 numbers 106 . However, a different study has found an increase in the number of c-Kit + ILCs in filaria-infected patients 107 .…”

Type 2 Cytokine Responses: Regulating Immunity to Helminth Parasites and Allergic Inflammation

“…Specifically, they reported that ATP-activated mast cells promote ILC2 responses via their secretion of IL-33 and that these events contribute to reduced parasite burdens (53). Additional studies report that ILC2s promote the differentiation of T H 2 cells following H. polygyrus infection via their secretion of IL-4(54), and preliminary reports suggest that ILC2s may contribute to host-protective responses against Strongyloides venezuelensis , T. muris and Schistosoma species(55–57). However, further studies are required to define the precise contribution of ILC2s in these infectious models.…”

Emerging roles of innate lymphoid cells in inflammatory diseases: Clinical implications

“…71,72 An expansion of CD117 + ILCs (ILC3s and subset of ILC2s) was found in blood of filarial-infected subjects, compared to filarial-uninfected controls. 71 Group 2 ILCs are diminished in young children infected with Schistosoma haematobium (bilharzia), whereby antihelminthic treatment resulted in increased TSLP levels and normalization of ILC2 numbers.…”

“…71 Group 2 ILCs are diminished in young children infected with Schistosoma haematobium (bilharzia), whereby antihelminthic treatment resulted in increased TSLP levels and normalization of ILC2 numbers. 72 …”