Helminth infections drive heterogeneity in human type 2 and regulatory cells

Karin de Ruiter, Simon P. Jochems, Dicky L. Tahapary, Koen A. Stam, Marion König, Vincent van Unen, Sandra Laban, Thomas Höllt, Moustapha Mbow, Boudewijn P.F. Lelieveldt, Frits Koning, Erliyani Sartono, Johannes W.A. Smit, Taniawati Supali, Maria Yazdanbakhsh

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

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.

Original languageEnglish
JournalScience Translational Medicine
Volume12
Issue number524
DOIs
Publication statusPublished - 1 Jan 2020

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