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Peer-reviewedCC BY 4.0Communications Biology

Long-term malaria exposure in pathogen-endemic environments is associated with distinct immune states

  • John Kimotho
  • Kioko Mwikali
  • Evans Mudibo
  • Michelle Muthui
  • Linda Murungi
  • Alfred Muia
  • Lynn Namwoso
  • Makobu Kimani
  • John Orimbo
  • Bernhards Ogutu
  • Daniel Muema
  • Thumbi Ndung’u
2 more authors
  • Martin K. Rono
  • Eunice W. Nduati
Open at sourcePDFDOICite

Abstract

Long-term exposure to malaria may shape baseline immune function, yet its effects in healthy adults remain unclear. Here we show that healthy Kenyan adults living in regions with higher malaria transmission and broader infectious exposure have distinct baseline immune profiles. Using blood-cell gene expression and circulating immune mediators from 60 adults across regions with differing malaria endemicity, we identify 658 differentially expressed genes. Higher exposure is associated with increased expression of pathways related to B-cell activation, antigen presentation, immune regulation, and post-transcriptional RNA processing, alongside reduced inflammatory, chemotactic, and vascular gene programmes. Circulating immune mediators are modestly elevated despite reduced inflammatory gene expression, indicating a partial dissociation between systemic mediator levels and cellular transcription. Our findings show that long-term malaria exposure in pathogen-endemic environments is associated with a distinct immune state characterised by adaptive immune activation and restrained inflammatory transcription, which may influence responses to subsequent infections and vaccination.

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Cite

BibTeXRIS
BibTeX
@article{kimotho2026longterm,
  title = {{Long-term malaria exposure in pathogen-endemic environments is associated with distinct immune states}},
  author = {John Kimotho and Kioko Mwikali and Evans Mudibo and Michelle Muthui and Linda Murungi and Alfred Muia and Lynn Namwoso and Makobu Kimani and John Orimbo and Bernhards Ogutu and Daniel Muema and Thumbi Ndung’u and Martin K. Rono and Eunice W. Nduati},
  journal = {Communications Biology},
  year = {2026},
  month = oct,
  doi = {10.1038/s42003-026-11101-2},
  url = {https://www.nature.com/articles/s42003-026-11101-2},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Long-term malaria exposure in pathogen-endemic environments is associated with distinct immune states
AU  - John Kimotho
AU  - Kioko Mwikali
AU  - Evans Mudibo
AU  - Michelle Muthui
AU  - Linda Murungi
AU  - Alfred Muia
AU  - Lynn Namwoso
AU  - Makobu Kimani
AU  - John Orimbo
AU  - Bernhards Ogutu
AU  - Daniel Muema
AU  - Thumbi Ndung’u
AU  - Martin K. Rono
AU  - Eunice W. Nduati
PY  - 2026
DA  - 2026/10/09
JO  - Communications Biology
DO  - 10.1038/s42003-026-11101-2
UR  - https://www.nature.com/articles/s42003-026-11101-2
AB  - Long-term exposure to malaria may shape baseline immune function, yet its effects in healthy adults remain unclear. Here we show that healthy Kenyan adults living in regions with higher malaria transmission and broader infectious exposure have distinct baseline immune profiles. Using blood-cell gene expression and circulating immune mediators from 60 adults across regions with differing malaria endemicity, we identify 658 differentially expressed genes. Higher exposure is associated with increased expression of pathways related to B-cell activation, antigen presentation, immune regulation, and post-transcriptional RNA processing, alongside reduced inflammatory, chemotactic, and vascular gene programmes. Circulating immune mediators are modestly elevated despite reduced inflammatory gene expression, indicating a partial dissociation between systemic mediator levels and cellular transcription. Our findings show that long-term malaria exposure in pathogen-endemic environments is associated with a distinct immune state characterised by adaptive immune activation and restrained inflammatory transcription, which may influence responses to subsequent infections and vaccination.
SN  - 2399-3642
ER  -