We have previously reported that supplementation with Saccharomyces cerevisiae fermentation products (SCFP) ameliorates clinical signs and lung pathology following experimental bovine respiratory syncytial virus (BRSV) infection in preweaned dairy calves. The objectives of this study were to determine the effect of SCFP supplementation on the metabolic and endocrine responses, and disease outcome of a viral-bacterial coinfection in preweaned calves. Twenty-seven, 1–2-d old Holstein-Angus cross calves were enrolled in the study; one SCFP calf was removed from the trial during the pre-challenge phase due to complications from nephritis. Calves were assigned to two treatment groups: control, or SCFP-treated, base milk replacer with 1 g/d SCFP (Smartcare, soluble formula) and calf starter top-dressed with 5 g/d SCFP (NutriTek, insoluble formula). Calves were infected with BRSV on d 21, followed 6 d later by intratracheal inoculation with Pasteurella multocida (PM). Calves were euthanized on d 10 post-viral infection. Calves receiving SCFP had reduced thoracic ultrasonography scores on d 7 post-viral infection (P = 0.03) and a tendency towards reduced scores on d 10-post viral infection (P = 0.09). Calves receiving SCFP also had less severe lung pathology scores at necropsy (P = 0.06). No differences between treatments were observed in lung viral loads (P = 0.48) or bacterial lung recovery (P = 0.34); however, there was a distinction in the lung location for PM recovery, with PM isolated more frequently from the cranial lobes in SCFP-treated calves, but more frequently from the caudal lobes of control calves. Calves treated with SCFP tended (P = 0.07) to have higher serum IL-6 concentrations following the coinfection. Calves treated with SCFP had lower concentrations of serum non-esterified fatty acids (NEFA) and beta-hydroxybutyric acid (BHB) compared to controls following experimental challenge (P = 0.03 and P = 0.08, respectively), suggesting metabolic changes favoring growth and development. There were no differences between groups in gene expression of insulin-receptor (INSR), insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R), growth hormone receptor (GHR), or haptoglobin in the liver. Results from this study suggest that supplementing with SCFP may moderate the impact of a respiratory viral-bacterial coinfection on preweaned calves through metabolic and immune modifications.

Innate immunity, initially thought to lack immunological memory, has been shown to have the capacity to be trained or to mount a heightened immune response towards an unrelated second challenge. The Bacillus Calmette Guerin vaccine, administered to prevent human and bovine tuberculosis, is one treatment that can induce innate immune memory. Here we evaluated the efficacy of BCG-induced innate training on the outcome of a respiratory virus challenge in pre-weaned calves. Groups of calves were given BCG Danish strain subcutaneously (or PBS as control). PBMCs and CD14+ monocytes were re-stimulated in-vitro with E. coli LPS (1μg/mL) or Pam3CSK4 (10μg/mL) at 2- and 4-weeks post-BCG respectively, and pro-inflammatory cytokine production was measured by ELISA. Calves were challenged via aerosol inoculation with BRSV at five weeks post-BCG. PBMCs from BCG calves showed enhanced IL-1b production upon in-vitro stimulation with LPS, and CD14+ monocytes from BCG calves showed increased IL-1b and IL-6 secretion. Alveolar macrophages from BCG calves showed enhanced cytokine production when re-stimulated with LPS. No significant changes were observed in clinical scores or viral burden between groups post BRSV challenge. Subcutaneous BCG administration can train bovine innate immune cells to exhibit a “memory-like” phenotype. Current efforts are focused on the characterization of epigenetic reprogramming in trained innate immune cells. Supported by grants from USDA, NIFA. R01 HD099104-01

Bovine respiratory disease is a complex syndrome which contributes to severe and often fatal pneumonia in beef and dairy cattle. Saccharomyces cerevisiae fermentation products (SCFP) are feed ingredients that have been previously shown to alter the immune response and outcome of a respiratory viral infection in calves. The objective of this study was to determine the effect of SCFP supplementation on the lung transcriptome in calves responding to a co-infection with bovine respiratory syncytial virus (BRSV) and Pasteurella multocida (PM). Twenty-eight, 1–2 day old calves were assigned to two groups: 1) control diet; or 2) SCFP treated diet. Calves were infected with BRSV on day 21, followed 6 days later by intratracheal inoculation with PM. Calves were euthanized on day 10 post-viral infection. There were no differences in viral or bacterial burden between treatment groups, but SCFP treated calves tended to have less severe lung pathology. Transcriptome analysis of lung tissue and bronchoalveolar lavage samples revealed over-represented genes related to membrane integrity, pathogen binding, and complement activation which presumably contributes to the host’s resiliency and response to the coinfection. Results from this study suggest that supplementing preweaned calves with SCFP may modulate the innate and adaptive immune response in mucosal sites. These findings will contribute to a better understanding of the underlying host response to bovine respiratory disease. Supported by funding from Diamond V Mills, Inc., Cedar Rapids, IA