Integrative multi-omics decoding of the host response to Klebsiella pneumoniae infection reveals an itaconate-centred metabolic-immune axis and a spatially organised inflammatory programme

Klebsiella pneumoniae infection in murine lung models triggers a coherent neutrophil inflammatory programme and a 30-fold pulmonary itaconate accumulation linked to spatially segregated metabolic niches.

• Why it matters: Existing single-omics profiles do not connect transcriptional, cellular, metabolic, and spatial host programmes into a unified molecular logic for infection.
• What they did: The authors harmonised 16 public datasets across RNA-seq, single-cell RNA-seq, metabolomics (1,842 features), and Visium spatial transcriptomics (~11,400 spots), then integrated them with WGCNA, CellChat, trajectory inference, deconvolution, and multi-model machine learning with 1,000x bootstrap validation.
• The result: A ten-gene hub signature (including IRG1 and S100A9) and a host-response classifier discriminated infected versus non-infected states with AUC 0.958 (discovery), 0.937 (internal validation), and 0.884–0.912 (external cohorts).

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