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

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.