Differential methanogenic archaea-induced TLR8-dependent signaling engages gene classes regulated by NF-κB p65 and STAT1/2.

Methanosphaera stadtmanae and Methanobrevibacter smithii trigger a shared TLR8-dependent immune program in human PBMCs, but M. stadtmanae induces earlier, stronger Class I gene activation.

• Why it matters: Archaea are common in the gut yet lack bacterial cell-wall ligands, so it is unclear how they engage innate immune signaling and shape distinct transcriptional programs.
• What they did: Human PBMCs were profiled by time-resolved RNA-seq after exposure to both archaea, followed by ChIP-qPCR for NF-κB p65 and STAT1/2 and dose-response testing using archaeal RNA inputs.
• The result: NF-κB p65 binding at Class I promoters is greater with M. stadtmanae, while STAT1/2 binding at Class II promoters occurs with both; input-tuned thresholds place Class II at lower RNA input and Class I at higher input.

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