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bioRxiv · 10.64898/2026.01.24.701481

Transcriptome of Peripheral Blood Mononuclear Cells Reveals Suppressed MAPK/AP-1 Pathways During Ascaris-Salmonella Coinfection in Pigs

Musimbi, Z. D.·Hayani, R.·Mugo, R. M.·Oser, L.·Schlosser-Brandenburg, J.·Rausch, S.·Hartmann, S.·Midha, A.
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Abstract

Ascaris and Salmonella are prevalent pathogens in pigs, and their coinfection could pose significant veterinary and public health concern. While Salmonella typically elicits strong monocyte-driven inflammation, we previously showed that A. suum coinfection impairs monocyte responses and increases bacterial burden. Building on these prior observations, we investigated the transcriptional basis of helminth-induced immune modulation using peripheral blood mononuclear cells from experimentally infected pigs. Bulk RNASeq analysis revealed 126 differentially expressed genes in coinfected pigs relative to Salmonella single-infected pigs, including downregulation of genes associated with chemotactic function (CCL3L1, CCL8, CXCL14) linked to monocyte recruitment and macrophage-mediated antimicrobial function. To uncover underlying cellular signaling mechanisms, we applied co-expression network analysis, identifying two modules of interest: one enriched for inflammatory signaling pathways (TNF, IL-17, MAPK), and the other associated with phagosome and lysosome function. Notably, coinfection resulted in selective repression of key genes in the inflammation-related module, including MAPK modulators (DUSP1, DUSP6), AP-1 components (FOS, NR4A1, MAFF), and monocyte activation genes (TNFSF9, CD163), pointing to a potential coordinated shutdown of monocyte inflammatory signaling. These findings reveal that an active Ascaris infection interferes with host immunity against a subsequent bacterial infection by disrupting AP-1/MAPK-dependent transcriptional networks, providing mechanistic insight into helminth-mediated immune modulation.

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Musimbi, Z. D., Hayani, R., Mugo, R. M., Oser, L., Schlosser-Brandenburg, J., Rausch, S., Hartmann, S., Midha, A.. 2026-01-26. Transcriptome of Peripheral Blood Mononuclear Cells Reveals Suppressed MAPK/AP-1 Pathways During Ascaris-Salmonella Coinfection in Pigs. https://doi.org/10.64898/2026.01.24.701481

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