Oser, L. | Search bioRxiv

bioRxiv2026

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

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.

immunology↗

bioRxiv2024

Concurrent Ascaris infection modulates host immunity resulting in impaired control of Salmonella infection in pigs

Ascaris is one of the most widespread helminth infections of humans and pigs, leading to chronic morbidity in humans and considerable economic losses in pig farming. Additionally, pigs are an important reservoir for the zoonotic bacterial pathogen Salmonella, where pigs can serve as asymptomatic carriers. Here, we investigated the impact of an ongoing Ascaris infection on the immune response to Salmonella in pigs. We observed higher bacterial burdens in experimentally coinfected pigs compared to pigs infected with Salmonella alone. Ascaris-infected pigs exhibited numerous hallmarks of a type 2 immune response in organs impacted by larval migration, including increased Th2 cells, increased IL-4 production, eosinophilia, and increased expression of CD206, a marker for alternatively activated macrophages. While we observed only mild changes in frequencies of CD4+ Treg, Ascaris- infected pigs had increased frequencies of CD8+ Treg. We show that type 2 immune signals enhance susceptibility of macrophages to Salmonella infection in vitro. Furthermore, Ascaris impaired Salmonella-induced monocytosis and TNF- production by myeloid cells. Hence, our data demonstrate widespread immunomodulation during an acute Ascaris infection that facilitates the microbial spread into gut-associated lymphoid tissue in a Salmonella coinfection. ImportanceIn experimentally infected pigs we show that an ongoing infection with the parasitic worm Ascaris suum modulates host immunity to render pigs more susceptible to invading Salmonella. Both infections are widespread in pig production and the prevalence of Salmonella is high in endemic regions of human Ascariasis, indicating that this is a clinically meaningful coinfection. We observed a type 2 immune response to be induced during an Ascaris infection correlating with an increased susceptibility of pigs to the concurrent bacterial infection.

immunology↗