Innate training induced by subcutaneous BCG administration in pre-weaned calves

Abstract 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