Transcriptional profiling of abomasal mucosa from young calves experimentally infected with Ostertagia ostertagi

Authors: BOSCHIERO, CLARISSA - University Of Maryland; Beshah, Ethiopia; BAKSHI, MARIAM - University Of Maryland; Miramontes, Eliseo; Hebert, Deborah; Thompson, Peter; Li, Congjun; ZHU, XIAOPING - University Of Maryland; ZARLENGA, DANTE - Former ARS Employee; Liu, Ge; Tuo, Wenbin

Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/24/2025
Publication Date: 3/4/2025
Citation: Boschiero, C., Beshah, E., Bakshi, M., Miramontes, E.N., Hebert, D.A., Thompson, P.C., Li, C., Zhu, X., Zarlenga, D., Liu, G., Tuo, W. 2025. Transcriptional profiling of abomasal mucosa from young calves experimentally infected with Ostertagia ostertagi. International Journal of Molecular Sciences. 26(5). Article e2264. https://doi.org/10.3390/ijms26052264.
DOI: https://doi.org/10.3390/ijms26052264

Interpretive Summary: Ostertagia ostertagi is the most pathogenic stomach worm causing significant production losses in cattle raising. Vaccination against this parasite is considered a valid alternative to the chemical drugs. However, very little is known about the immune responses elicited by this worm. We used RNA sequencing technology to determine changes of all genes in the bovine stomach. Animals were infected with O. ostertagi Stage 3 larvae and euthanized on 3 - 21 days post infection to collect stomach tissues for RNS extraction. Uninfected calves were used as controls. Our study showed that differentially expressed genes (DEGs, genes that are either significantly up- and down-regulated) are detected between 3-21 days post infection. Different parts of the stomach also expressed different DEGs. The highly regulated genes are associated with biological processes including immunity and immunosuppression, cellular reorganization, and cell migration and proliferation. The data collectively indicate that the stomach worm can stimulate host immune responses. Yet, the parasite is also able to evade host immunity by upregulating immune suppression genes. The knowledge of mechanisms of parasite evasion can aid in rational design of vaccines against the parasite. The information from this research is useful to researchers and veterinarians.

Technical Abstract: Ostertagia ostertagi, also known as the brown stomach worm, causes significant pathology in the abomasum, resulting in production and nutritional losses in cattle. Alternative control measures, such as vaccination, are urgently needed because of rapidly growing anthelmintic drug resistance. There is a need to understand host responses to the infection, especially immune responses, to advance vaccine discovery and design. Therefore, the present study investigated comprehensive changes in gene transcription in the abomasal mucosa of cattle infected with O. ostertagi at 0, 3–5, 7–9, 10, and 21 days post-infection (dpi) using RNA sequencing (RNA-seq). Compared to uninfected controls, infected animals exhibited significant increases in differentially expressed genes (DEGs) throughout the infection period. Infection induced more upregulated than downregulated genes in the abomasal fundic mucosa (FUN) when compared to the abomasal pyloric mucosa (PYL). The largest transcriptional changes occurred between 7–9 and 10 dpi during the final development of the L4 and their emergence from the gastric glands. Most DEGs are associated with host immunity, cellular reorganization, cell migration, and proliferation. Tuft/epithelial cell response to the infection was atypical, lacking an anticipated increase in key alarmin cytokine genes. Numerous genes associated with T helper (Th) 1, Th2, and Th17 responses and T cell exhaustion were upregulated, suggesting altered immune regulation. The data collectively indicate that O. ostertagi infection elicits massive host responses, particularly immune responses, which are intertwined with the parasite’s disruption of abomasal function, which likely impairs the nutrient utilization of the host. The infection is characterized by the absence of a dominant Th response and displaying a mixed activation of Th1, Th2, and Th17 pathways. Elevated expression of T cell exhaustion genes and lack of increase in epithelial alarmin cytokine genes suggest a downregulation of, or a deficiency in initiating, effective host immunity to the infection. Understanding mechanisms of parasite-mediated immune evasion and their nutritional consequences will facilitate the rational design of protective vaccines against infections of complex nematode parasites.