Intranasal zinc and vitamin A treatments alter response to bovine respiratory syncytial virus and <i>Mannheimia haemolytica</i> co-infection

During disease, there may be increased local demands for zinc (Zn) and vitamin A to support pathogen response. This study evaluates the effects of intranasal Zn and vitamin A treatments on steers experimentally infected with bovine respiratory disease (BRD) pathogens, bovine respiratory syncytial virus (BRSV) and <i>Mannheimia haemolytica</i>, hypothesizing that steers treated with Zn and vitamin A (VA) will have improved recovery to BRD challenge. Forty-eight Angus crossbred steers (333 ± 4.2 kg) were utilized in two groups with identical challenge timelines. The day prior to challenge (d -1), steers were shipped for 6 hours. On d 0, steers were administered an aerosol inoculation with ~10⁴ TCID₅₀/mL BRSV strain 375 followed by an intratracheal inoculation with <i>M. haemolytica</i> (1.42 × 10⁸ CFU strain D153, serotype A1) on d 5. On d 4, steers received intranasal treatments: zinc (IN ZN; 50 mg Zn oxide nanoparticles), vitamin A (IN VA; 200,000 IU as retinyl palmitate), a combination of zinc (50 mg) and vitamin A (200,000 IU; IN VA + ZN) or no treatment (CON). Statistics were analyzed using the Mixed procedure of SAS 9.4 (Cary, NC) and contrast statements were utilized to determine the effects of Zn, VA and intranasal treatment. Disease challenge resulted in mostly mild, subclinical signs of disease. There was an interaction for plasma VA (TRT × Day <i>P</i> < 0.01) where VA treated steers (IN VA and IN VA + ZN) had sustained plasma VA concentrations on d 5, when ZN and CON had decreased plasma VA. After challenge (d 19), liver VA concentrations were increased in IN VA (IN VA <i>P</i> = 0.03) and IN ZN (IN ZN <i>P</i> = 0.05) treated steers. Zn treated steers (ZN and ZN + VA) tended to have increased gene expression of <i>matrix metalloproteinase 9</i> (<i>P</i> = 0.06) on d 5 and <i>cellular retinol binding protein 1</i> (<i>P</i> = 0.08) on d 7 in cells collected from nasopharyngeal swabs. Additionally, immune cell populations from bronchoalveolar lavage were altered with increased CD11b expression on neutrophils (IN VA <i>P </i>= 0.01) and CD11c on macrophages (IN ZN <i>P</i> = 0.08) on d 7. During a mild disease challenge, intranasal Zn and VA treatments impacted lung inflammatory environment and nutritional immunity, suggesting potential benefits in mild or deficient nutritional statuses.