Leiden University Scholarly Publications

Manurung, M.D.; Sonnet, F.; Hoogerwerf, M.A.; Janse, J.J.; Kruize, Y.; Bes-Roeleveld, L.D.; ... ; Yazdanbakhsh, M. (2024)

Controlled human hookworm infection remodels plasmacytoid dendritic cells and regulatory T cells towards profiles seen in natural infections in endemic areas

Article / Letter to editor

Hookworm infection remains a significant public health concern, particularly in low- and middle-income countries, where mass drug administration has not stopped reinfection. Developing a vaccine is crucial to complement current control measures, which necessitates a thorough understanding of host immune responses. By leveraging controlled human infection models and high-dimensional immunophenotyping, here we investigated the immune remodeling following infection with 50 Necator americanus L3 hookworm larvae in four naïve volunteers over two years of follow-up and compared the profiles with naturally infected populations in endemic areas. Increased plasmacytoid dendritic cell frequency and diminished responsiveness to Toll-like receptor 7/8 ligand were observed in both controlled and natural infection settings. Despite the increased CD45RA⁺ regulatory T cell (T_regs) frequencies in both settings, markers of T_regs function, including...Show moreHookworm infection remains a significant public health concern, particularly in low- and middle-income countries, where mass drug administration has not stopped reinfection. Developing a vaccine is crucial to complement current control measures, which necessitates a thorough understanding of host immune responses. By leveraging controlled human infection models and high-dimensional immunophenotyping, here we investigated the immune remodeling following infection with 50 Necator americanus L3 hookworm larvae in four naïve volunteers over two years of follow-up and compared the profiles with naturally infected populations in endemic areas. Increased plasmacytoid dendritic cell frequency and diminished responsiveness to Toll-like receptor 7/8 ligand were observed in both controlled and natural infection settings. Despite the increased CD45RA⁺ regulatory T cell (T_regs) frequencies in both settings, markers of T_regs function, including inducible T-cell costimulatory (ICOS), tumor necrosis factor receptor 2 (TNFR2), and latency-associated peptide (LAP), as well as in vitro T_regs suppressive capacity were higher in natural infections. Taken together, this study provides unique insights into the immunological trajectories following a first-in-life hookworm infection compared to natural infections.Show less

All authors

Manurung, M.D.; Sonnet, F.; Hoogerwerf, M.A.; Janse, J.J.; Kruize, Y.; Bes-Roeleveld, L.D.; König, M.; Loukas, A.; Dewals, B.G.; Supali, T.; Jochems, S.P.; Roestenberg, M.; Coppola, M.; Yazdanbakhsh, M.

Date

2024-07-16

Journal

Nature Communications

Volume

15

Issue

1

DOI

doi:10.1038/s41467-024-50313-0

Link

http://www.nature.com/articles/s41467-024-50313-0