Authors: Mikhael D. Manurung, Friederike Sonnet, Marie-Astrid Hoogerwerf, Jacqueline J. Janse, Yvonne Kruize, Laura de Bes-Roeleveld, Marion König, Alex Loukas, Benjamin G. Dewals, Taniawati Supali, Simon P. Jochems, Meta Roestenberg, Mariateresa Coppola, Maria Yazdanbakhsh
Published: 2024-07-16
DOI: 10.1038/s41467-024-50313-0
Source: Full article
AbstractHookworm 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 (Tregs) frequencies in both settings, markers of Tregs function, including inducible T-cell costimulatory (ICOS), tumor necrosis factor receptor 2 (TNFR2), and latency-associated peptide (LAP), as well as in vitro Tregs 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.