Host- and genotype-specific transcriptomic responses to Mycoplasma bovis infection in bison and Holstein peripheral blood mononuclear cells

Authors: Kaplan, Bryan; Sarlo Davila, Kaitlyn; SLATE, JAMISON - Oak Ridge Institute For Science And Education (ORISE); Olsen, Steven; Dassanayake, Rohana; Holthausen, David; Nielsen, Daniel; Sacco, Randy

Submitted to: Frontiers in Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/13/2026
Publication Date: 8/6/2026
Citation: Kaplan, B.S., Sarlo Davila, K.M., Slate, J.R., Olsen, S.C., Dassanayake, R.P., Holthausen, D.J., Nielsen, D.W., Sacco, R.E. 2026. Host- and genotype-specific transcriptomic responses to Mycoplasma bovis infection in bison and Holstein peripheral blood mononuclear cells. Frontiers in Immunology. 17. Article 1873273. https://doi.org/10.3389/fimmu.2026.1873273.
DOI: https://doi.org/10.3389/fimmu.2026.1873273

Interpretive Summary: Mycoplasma bovis (M. bovis), a bacteria, is a significant cause of respiratory disease in cattle and bison. M. bovis was first identified in the 1960's during a time when Holstein dairy cows were undergoing intensive selective breeding to increase milk production. This genetic selection produced contemporary Holsteins (CH) that have increased milk production in addition to an increase in disease susceptibility compared to unselected Holsteins (UH). In cattle, M. bovis causes a chronic respiratory disease that is frequently associated with the Bovine Respiratory Disease Complex, a multifactorial disease complex. In bison, M. bovis alone can cause respiratory disease. The objective of this study was to compare the gene expression of bison and Holstein peripheral blood mononuclear cells to better understand the host response to M. bovis. Our results show UH cells had the greatest response to M. bovis infection while bison cells had the lowest response. Despite this, bison cells displayed the greatest expression of pro-inflammatory genes that may cause excessive tissue damage during M. bovis infection in this species.

Technical Abstract: The bacterial pathogen Mycoplasma bovis (M. bovis) emerged as the etiologic agent of mastitis in cattle during the early 1960’s. Concurrent to the emergence of M. bovis, Holsteins in the US were undergoing intensive genetic selection for increased milk production. Comparison studies with unselected Holsteins have found an association with selection and increased susceptibility to disease. More recently, M. bovis was identified as the cause of epizootics of severe, chronic respiratory disease in American bison (Bison bison). In cattle, M. bovis causes chronic respiratory disease and is associated with the bovine respiratory disease complex while in bison, M. bovis is considered a primary pathogen. The objective of this study was to characterize and compare the transcriptomic response of peripheral blood monocytes from contemporary Holsteins (CH), unselected Holsteins (UH), and bison at 24 hr following M. bovis infection. The greatest and fewest number of differentially expressed genes (DEG) were observed in UH and bison, respectively. Ingenuity pathway analysis of DEG identified the genotype-specific expression of pathways involved in cytokine and chemokine response, neutrophil degranulation, and antigen processing and presentation. This study is the first to demonstrate the PBMC transcriptomic response to M. bovis infection differs by genotype and species. These findings potentially explain the differences observed in clinical disease between bison and cattle and highlight the effects of selection for milk production on the Holstein response to M. bovis.