Format

Send to

Choose Destination
Sci Transl Med. 2020 Jan 1;12(524). pii: eaaw3703. doi: 10.1126/scitranslmed.aaw3703.

Helminth infections drive heterogeneity in human type 2 and regulatory cells.

Author information

1
Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.
2
Department of Internal Medicine, Division of Endocrinology, Dr. Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia, 10430 Jakarta, Indonesia.
3
Metabolic, Cardiovascular and Aging Cluster, The Indonesian Medical Education and Research Institute, Universitas Indonesia, 10430 Jakarta, Indonesia.
4
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.
5
Computer Graphics and Visualization Group, Delft University of Technology, 2628 XE Delft, Netherlands.
6
Computational Biology Center, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.
7
Department of Immunology, Cheikh Anta Diop University of Dakar (UCAD), 5005 Dakar, Senegal.
8
Department of LKEB Radiology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.
9
Department of Pattern Recognition and Bioinformatics Group, Delft University of Technology, 2628 XE Delft, Netherlands.
10
Department of Internal Medicine, Radboud University Medical Centre, 6525 GA Nijmegen, Netherlands.
11
Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, Netherlands.
12
Department of Parasitology, Faculty of Medicine Universitas Indonesia, 10430 Jakarta, Indonesia.
13
Department of Parasitology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands. m.yazdanbakhsh@lumc.nl.

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.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center