Alternatives to Antibiotics: neonatal immunomodulation to improve disease resistance in animals

Authors: Loving, Crystal; Byrne, Kristen; SAMUEL, BEULAH ESTHER - Iowa State University; WANGARI, TERESIA - Iowa State University; TUGGLE, CHRISTOPHER - Iowa State University; MCGILL, JODI - Iowa State University

Submitted to: Conference Research Workers Disease Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 1/20/2023
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Objective A potential immunomodulation mechanism for improving disease resilience is innate training, which relies on epigenetic modifications of immune cells for a heightened (ie, trained) response upon repeated microbial stimulation. Prior experiences indicate bacillus Calmette-Guerin (BCG) exposure increases cytokine production upon secondary exposure to microbe-associated molecular patterns, and epidemiological data suggest improved disease resistance in humans administered neonatal BCG. Methods Neonatal piglets received BCG or mock inoculum via intravenous (IV) route and were subsequently challenged with influenza A virus (IAV). Calves received intramuscular BCG or mock inoculum and were subsequently challenged with respiratory syncytial Virus (RSV). Body temperature was recorded and nasal swabs collected through the acute phase of viral infection. At necropsy, gross lung pathology was assessed. In addition, prior to IAV or RSV challenge, peripheral mononuclear cells were isolated from mock and BCG inoculated animals and stimulated in vitro with LPS to evaluate in vivo induction of a trained phenotype via cytokine production and gene expression. Results Upon in vitro LPS exposure, monocytes isolated from IV BCG treated piglets produced more IL-1beta and TNFa cytokine than monocytes from mock pigs, indicating a trained phenotype. However, no significant differences in clinical presentation or nasal and lung viral titers were detected. Upon in vitro LPS exposure, monocytes isolated from calves after IM BCG administration produced more IL-1beta and IL-6 cytokine than monocytes from mock calves. Yet, no significant differences were detected in RSV shedding or lung titers. Transcriptomic response of porcine monocytes is under evaluation, as well as epigenetic evaluation of porcine and bovine monocytes and bovine gamma delta T cells. Conclusions BCG administration induced a trained phenotype in porcine and bovine peripheral cells. However, it did not translate into a significant change in respiratory viral infection. Trials are ongoing to assess protection again bacterial infection in pigs and cattle.