Systems analysis unravels a common rural-urban gradient in immunological profile, function, and metabolic dependencies
Urbanization affects environmental exposures and lifestyle, shaping immune system variation and influencing disease susceptibility and vaccine responses. Here, we present systems analysis of immune profiles across the rural-urban gradient, comparing rural and urban Senegalese with urban Dutch individuals. By integrating single-cell phenotyping, metabolic profiling, and functional analysis, we reveal a trajectory of immune remodeling along the gradient. This includes enrichment of proinflammatory CD11c<sup>+</sup> B cells associated with altered IgG Fc glycosylation, adaptive NK cells with reduced responsiveness to accessory cytokines, and CD161<sup>+</sup>CD4<sup>+</sup>T cells with enhanced cytokine production in rural settings. Metabolic perturbation studies demonstrated distinct dependencies on glycolysis, pentose phosphate pathway, and fatty acid synthesis for cellular cytokine responses across populations. We validate core rural-urban immune signatures in an independent Indonesian cohort, suggesting shared immunological adaptations to urbanization across ancestries and geographical areas. Our findings provide insights into rural-urban immune function in understudied populations.
Authors
- Dicky L. Tahapary (ORCID: https://orcid.org/0000-0002-4048-5159)
- Ahmed Mahfouz (ORCID: https://orcid.org/0000-0001-8601-2149)
- Tom Veldhuizen
- Taniawati Supali (ORCID: https://orcid.org/0000-0002-1209-402X)
- Susan L. Kloet (ORCID: https://orcid.org/0000-0001-9189-0640)
- Graham A. Heieis (ORCID: https://orcid.org/0000-0001-9864-7272)
- Mikhael D. Manurung (ORCID: https://orcid.org/0000-0003-2728-1829)
- Maria Yazdanbakhsh (ORCID: https://orcid.org/0000-0002-7666-1441)
- Shohreh Azimi (ORCID: https://orcid.org/0000-0002-3117-5722)
- Marion König (ORCID: https://orcid.org/0000-0002-9892-218X)
- Malick Ndao
- Cornelis H. Hokke (ORCID: https://orcid.org/0000-0003-3545-7804)
- Yvonne C. M. Kruize
- Pytsje T. Hoekstra (ORCID: https://orcid.org/0000-0002-7285-9223)
- Linda J. Wammes (ORCID: https://orcid.org/0000-0002-6660-9738)
- Dennis Hoving (ORCID: https://orcid.org/0000-0002-9246-5774)
- Manfred Wuhrer (ORCID: https://orcid.org/0000-0002-0814-4995)
- Simon P. Jochems (ORCID: https://orcid.org/0000-0002-4835-1032)
- Roberta Menafra (ORCID: https://orcid.org/0000-0002-5266-0639)
- Bart Everts (ORCID: https://orcid.org/0000-0002-3764-5131)
- Marouba Cisse (ORCID: https://orcid.org/0000-0001-5359-7451)
- Souleymane Mboup (ORCID: https://orcid.org/0000-0002-7968-3320)
- Moustapha Mbow (ORCID: https://orcid.org/0000-0002-5745-2628)
- Alioune Dièye
Institutions
- Leiden University Medical Center (NL)
- University of Indonesia (ID)
- Netherlands Metabolomics Centre (NL)
- Institute of Health Research, Epidemiological Surveillance and Training (SN)
- Cheikh Anta Diop University (SN)
Publication Details
- Journal
- Science Advances
- Published
- 2025-05-01
- DOI
- https://doi.org/10.1126/sciadv.adu0419
- Citations
- 3
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 2.39