Research ArticlePARASITIC INFECTIONS

Helminth infections drive heterogeneity in human type 2 and regulatory cells

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Science Translational Medicine  01 Jan 2020:
Vol. 12, Issue 524, eaaw3703
DOI: 10.1126/scitranslmed.aaw3703

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Parasite perturbation of immunity

Helminths infect billions of people and are known to modulate host immune responses to promote their survival. De Ruiter et al. used mass cytometry to gain a better understanding of which cells are affected by helminth infection. They analyzed samples from rural Indonesians before and after deworming treatment. These were compared to samples from Europeans and urban Indonesians, neither of which had been exposed to helminths. Helminths expanded specific type 2 and regulatory cells; many immune alterations reverted upon deworming. These details on host-pathogen interaction could inform future targeted therapies.

Abstract

Helminth infections induce strong type 2 and regulatory responses, but the degree of heterogeneity of such cells is not well characterized. Using mass cytometry, we profiled these cells in Europeans and Indonesians not exposed to helminths and in Indonesians residing in rural areas infected with soil-transmitted helminths. To assign immune alteration to helminth infection, the profiling was performed before and 1 year after deworming. Very distinct signatures were found in Europeans and Indonesians, showing expanded frequencies of T helper 2 cells, particularly CD161+ cells and ILC2s in helminth-infected Indonesians, which was confirmed functionally through analysis of cytokine-producing cells. Besides ILC2s and CD4+ T cells, CD8+ T cells and γδ T cells in Indonesians produced type 2 cytokines. Regulatory T cells were also expanded in Indonesians, but only those expressing CTLA-4, and some coexpressed CD38, HLA-DR, ICOS, or CD161. CD11c+ B cells were found to be the main IL-10 producers among B cells in Indonesians, a subset that was almost absent in Europeans. A number of the distinct immune profiles were driven by helminths as the profiles reverted after clearance of helminth infections. Moreover, Indonesians with no helminth infections residing in an urban area showed immune profiles that resembled Europeans rather than rural Indonesians, which excludes a major role for ethnicity. Detailed insight into the human type 2 and regulatory networks could provide opportunities to target these cells for more precise interventions.

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