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<p>Host-pathogen interactions are shaped by the nature of the pathogen and by host-related factors. Human host responses can be characterized in microbe-stimulated immune cells using transcriptomics. We set out to characterize gene expression changes as a result of microbial in vitro stimulation in medium-cultured human primary immune cells, using four pathogen ligands representing bacteria (LPS and <i>S. aureus</i>), viruses (Poly(I:C)) and fungi (<i>C. albicans</i>) for 4 and 24 h, resulting in a total of 52 samples for analysis. We analyze the transcriptional changes on gene and pathway levels, highlighting common and distinct effects of pathogen stimulation. We highlight genes without a known function that were differentially expressed as a common effect of pathogen stimulation. Amongst those, we find uncharacterized genes such as <i>KIAA0040</i> and <i>CYRIA</i> to be co-expressed with genes involved in innate immunity and downstream signaling from the PRRs, respectively. Further linking our differential expression data to IEI, we identify 901 variants in uncharacterized genes in a cohort of patients with rare immune disorders, prioritizing 5 candidate variants in 4 genes that could underlie these diseases. Our results therefore indicate a potential role of these genes in the human immune response and provide further candidate variants for rare immune-mediated diseases.</p>

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Transcription-based identification of uncharacterized genes in the human immune response

  • 期刊论文

  • 发表日期：

    2026年5月12日

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  • Emil E. Vorsteveld,
  • Simone Kersten,
  • Charlotte Kaffa,
  • Annet Simons,
  • Peter A. C. ’t Hoen,
  • Mihai G. Netea,
  • Alexander Hoischen

摘要

Host-pathogen interactions are shaped by the nature of the pathogen and by host-related factors. Human host responses can be characterized in microbe-stimulated immune cells using transcriptomics. We set out to characterize gene expression changes as a result of microbial in vitro stimulation in medium-cultured human primary immune cells, using four pathogen ligands representing bacteria (LPS and S. aureus), viruses (Poly(I:C)) and fungi (C. albicans) for 4 and 24 h, resulting in a total of 52 samples for analysis. We analyze the transcriptional changes on gene and pathway levels, highlighting common and distinct effects of pathogen stimulation. We highlight genes without a known function that were differentially expressed as a common effect of pathogen stimulation. Amongst those, we find uncharacterized genes such as KIAA0040 and CYRIA to be co-expressed with genes involved in innate immunity and downstream signaling from the PRRs, respectively. Further linking our differential expression data to IEI, we identify 901 variants in uncharacterized genes in a cohort of patients with rare immune disorders, prioritizing 5 candidate variants in 4 genes that could underlie these diseases. Our results therefore indicate a potential role of these genes in the human immune response and provide further candidate variants for rare immune-mediated diseases.