Bovine respiratory disease (BRD) causes morbidity and mortality in cattle of all ages. Supplementing with postbiotic products from Saccharomyces cerevisiae fermentation (SCFP) has been reported to improve growth and provide metabolic support required for immune activation in calves. The objective of this study was to determine effects of SCFP supplementation on the transcriptional response to
coinfection with bovine respiratory syncytial virus (BRSV) and Pasteurella multocida (PM) in the lung using
RNA seq. Twenty-three calves were enrolled and assigned to 2 treatment groups: control (CON, n = 12) or SCFP-treated (SCFP, n = 11, fed 1 g/d SmartCare® in milk and 5 g/d NutriTek on starter grain). Calves were infected with ∼104 TCID50 BRSV, followed 6 d later by intratracheal inoculation with ∼1010 cfu of PM (strain P1062). Calves were euthanized on d 10 post
viral infection. Blood cells were collected and assayed on d 0 and 10 after
viral infection. Bronchoalveolar lavage (BAL) cells were collected and assayed on d 14 of the feeding period (preinfection) and d 10 after
viral infection. Blood and BAL cells were assayed for proinflammatory
cytokine production in response to stimulation with
lipopolysaccharide (LPS) or a combination of
Poly(I:C) and
Imiquimod, and BAL cells were evaluated for phagocytic and
reactive oxygen species (ROS) production capacity. Antemortem and postmortem BAL and lesion (LL) and non-lesioned (NLL) lung tissue samples collected at necropsy were subjected to
RNA extraction and sequencing. Sequencing reads were aligned to the bovine reference genome (UMD3.1) and EdgeR used for differential gene expression (DEGs) analysis. Supplementation with SCFP did not affect the respiratory burst activity or phagocytic activity of either lung or blood immune cells. Immune cells from the peripheral blood of SCFP supplemented calves produced increased quantities of
interleukin (IL)-6 in response to
toll-like receptor stimulation, while cells from the BAL of SCFP-treated calves secreted less proinflammatory
cytokines,
tumor necrosis factor-α (TNF-α) and
IL-6 in response to the same stimuli. Transcriptional responses in lung tissues and BAL samples from SCFP calves differed from CON. The top enriched pathways in SCFP-treated lungs were associated with decreased expression of inflammatory responses and increased expression of
plasminogen and genes involved in
glutathione metabolism, supporting effective lung repair. Our results indicate that supplementing with SCFP postbiotics modulates both systemic and mucosal immune responses, leading to increased resistance to BRD.