Host transcriptome response to Mycoplasma bovis and bovine viral diarrhea virus in bovine tissues

Authors: Zakrzewicz, Anna; Atchison, Randy; FALKENBERG, SHOLLIE - Auburn University; Dassanayake, Rohana; NIELL, JOHN - Retired ARS Employee; Casas, Eduardo

Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/28/2025
Publication Date: 4/10/2025
Citation: Zakrzewicz, A.K., Atchison, R.G., Falkenberg, S.M., Dassanayake, R.P., Niell, J.D., Casas, E. 2025. Host transcriptome response to Mycoplasma bovis and bovine viral diarrhea virus in bovine tissues. BMC Genomics. 26. Article 361. https://doi.org/10.1186/s12864-025-11549-2.
DOI: https://doi.org/10.1186/s12864-025-11549-2

Interpretive Summary: Mycoplasma bovis (M. bovis) is a pathogen associated with respiratory disease in cattle. Respiratory illness in cattle often involves infection with more than one bacteria or virus. A viral infection can weaken the animal's immune system and make it easier for bacteria to cause further infection. The objective of this study was to identify if there are differences in the expression of genes in immune related tissues or in blood when animals are challenged with M. bovis, or with both M. bovis and bovine viral diarrhea virus (BVDV). The calves in this study were assigned to three treatment groups: Control (no infection) M. bovis (M. bovis infection), and a dual group (infected with M. bovis and BVDV). Thymus and spleen showed the greatest differences in gene expression due to challenge. In liver, tracheal-brochial lymph node, spleen, and thymus, the dual treatment had a greater impact on gene expression than M. bovis alone. The differentially expressed genes identified in this study could potentially be used to design new vaccines.

Technical Abstract: Background: Mycoplasma bovis is a prominent pathogen associated with respiratory disease in livestock. Respiratory disease in cattle often involves co-infection, where a primary viral infection can weaken the host immune system and thus enhance subsequent bacterial infection. The objective of this study was to investigate changes in the host (cattle) transcriptome during bacterial-viral co-infection. RNA sequencing was done in whole blood cells (WBC), liver, mesenteric lymph node (MLN), tracheal-bronchial lymph node (TBLN), spleen, and thymus collected from Control animals (n =2), animals infected with M. bovis (MB; n = 3), and animals infected with M. bovis and bovine viral diarrhea virus (BVDV) (Dual; n = 3). Results: Thymus and spleen had the greatest number of differentially expressed genes (DEGs) out of all tissues analyzed. In spleen, genes involved in maintenance of the extracellular matrix (ECM) including collagen type XV alpha 1 chain (COL15A1), collagen type IV alpha 2 chain (COL4A2), and heparan sulfate proteoglycan 2 (HSPG2) were the most significantly downregulated in Dual compared to Control and MB. In thymus, complement 3 (C3) was a highly significant DEG and upregulated in Dual compared to Control and MB. Interferon alpha inducible protein 6 (IFI6) and interferon-induced transmembrane proteins (IFITM1 and IFITM3), were significantly associated with infection status and upregulated in spleen and thymus of Dual compared to Control and MB. Conclusion: Downregulation of ECM components may cause degradation of the ECM and contribute to increased viral spread due to co-infection. Hyperactivation of complement pathway genes may contribute to damage to the thymus and influence severity of co-infection. Co-expression of IFI6, IFITM1 and IFITM3 across lymphoid tissues may be connected to enhanced pathogenesis in co-infection. These findings suggest co-infection exacerbates disease severity through modulation of ECM components in spleen and complement and coagulation cascades in the thymus. These impacted pathways may underlie thymic atrophy and impaired pathogen clearance due to BVDV and M. bovis co-infection.