Comparative innate immune responses of bison and cattle to Mannheimia haemolytica wildtype and LPS sialylation-deficient mutant strain

Authors: MENGHWAR, HARISH - Oak Ridge Institute For Science And Education (ORISE); Boggiatto, Paola; Olsen, Steven; SLATE, JAMISON - Oak Ridge Institute For Science And Education (ORISE); Zakrzewicz, Anna; Kanipe, Carly; Kaplan, Bryan; Nielsen, Daniel; Tatum, Fred; Casas, Eduardo; Dassanayake, Rohana

Submitted to: Research in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/9/2025
Publication Date: 6/10/2025
Citation: Menghwar, H., Boggiatto, P.M., Olsen, S.C., Slate, J., Goldkamp, A.K., Kanipe, C.R., Kaplan, B.S., Nielsen, D.W., Tatum, F.M., Casas, E., Dassanayake, R.P. 2025. Comparative innate immune responses of bison and cattle to Mannheimia haemolytica wildtype and LPS sialylation-deficient mutant strain. Research in Veterinary Science. 193. Article 105764. https://doi.org/10.1016/j.rvsc.2025.105764.
DOI: https://doi.org/10.1016/j.rvsc.2025.105764

Interpretive Summary: Mannheimia haemolytica is the primary bacterial etiological agent of bovine respiratory disease complex (BRDC) resulting in significant economic losses to the U.S. beef and dairy cattle industry. Although bison are also sensitive to fatal pneumonia caused by M. haemolytica, the prevalence of BRDC is uncommon. Differential susceptibility of cattle and bison to M. haemolytica infection is unknown. Therefore, it is important to understand how M. haemolytica can make bison sick. Our study shows that cells capable of engulfing and absorbing bacteria and other small cells and particles (phagocytes) and complement of bison can effectively kill M. haemolytica mutants but not the wild-type parental strain, similar to cattle. Therefore, understanding the immune response of bison to M. haemolytica will assist us developing new vaccines.

Technical Abstract: Cattle macrophages possess an enhanced ability to phagocytose and kill Escherichia coli compared to American bison (Bison bison) macrophages. However, it remains unclear whether observed phagocytic differences between the two related ruminant species are restricted to E. coli. Although not frequently reported, bison are susceptible to pneumonia caused by Mannheimia haemolytica. Previously, we showed that M. haemolytica LPS sialylation-deficient mutant ('neuA) was more sensitive to phagocytic (neutrophils and monocytes) and complement-mediated killing than were the wildtype parent strain. Therefore, the goal of this study was to compare the phagocytic- and complement-mediated killing of M. haemolytica wildtype and 'neuA strains between bison and cattle. Relatively higher percentages of reactive oxygen species positive neutrophils and monocytes were found in cattle compared to bison. Significant uptake of M. haemolytica wildtype and 'neuA mutant strains by both monocytes and neutrophils in cattle were observed, compared to bison as assessed by flow cytometry (p < 0.05). However, both species showed similar phagocytic- and complement-mediated killing in which 'neuA mutant was more sensitive to killing than the wildtype strain (p < 0.0001). Complement-mediated 'neuA mutant killing disappeared in both species when the serum was heat inactivated. Taken together, these findings suggested that despite differences in phagocytosis efficiencies and uptake, there is no significant difference between phagocytic- and complement-mediated killing of M. haemolytica 'neuA mutant between two related ruminant species.