Nature Communications· 2026Q1
Differential methanogenic archaea-induced TLR8-dependent signaling engages gene classes regulated by NF-κB p65 and STAT1/2
- 1citations
- Q1SCImago
- 2026year
Short summary
Methanosphaera stadtmanae and Methanobrevibacter smithii induce distinct immune programs in human PBMCs via TLR8, with M. stadtmanae triggering an earlier, stronger response (Class I genes) linked to greater NF-κB p65 binding, while both induce Class II genes via STAT1/2 binding.
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Key points
- M. stadtmanae and M. smithii induce distinct immune programs in human PBMCs with different kinetics.
- Responses to both archaea are broadly TLR8-dependent.
- M. stadtmanae's stronger early response (Class I genes) correlates with greater NF-κB p65 promoter binding.
- STAT1/2 binding at Class II promoters occurs with both M. stadtmanae and M. smithii.
- Immune response thresholds are input-tuned, with Class II genes induced by lower RNA input and Class I genes by higher input.
AI-generated from the title and abstract; the full text is not read.
Abstract
Abstract Archaea are prevalent in the human gut but lack canonical bacterial cell wall-associated immune ligands. Time-resolved RNA-seq of human PBMCs showed that Methanosphaera stadtmanae and Methanobrevibacter smithii induced a shared immune program but with distinct kinetics: M. stadtmanae triggered an earlier and stronger response, whereas M. smithii acted more gradually. Conserved early-upregulated genes separated into Class I genes, preferentially induced by M. stadtmanae , and Class II genes, similarly induced by both. M. stadtmanae showed greater early uptake, while responses to both archaea were broadly TLR8-dependent. ChIP-qPCR linked the stronger Class I gene activation induced by M. stadtmanae to greater NF-κB p65 binding at Class I promoters, whereas STAT1/2 binding at Class II promoters occurred with both stimuli. Dose-response analyses with archaeal RNA inputs supported distinct activation thresholds, with Class II genes at lower input and Class I genes requiring higher input. Together, these findings support an input-tuned TLR8-dependent mechanism shaping differential immune programs towards archaea.
The authors' abstract, as published at the source. Nature Communications, 2026 · DOI ↗
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ImmunologyImmunology and Microbiology