Affiliation:
1. *Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA
2. †Cargill Animal Nutrition, Elk River, MN
Abstract
Abstract
The bacillus Calmette–Guérin (BCG) vaccine, administered to prevent tuberculosis, is a well-studied inducer of trained immunity in human and mouse monocytes. We have previously demonstrated that aerosol BCG administration induces innate training in calves. The current study aimed to determine whether s.c. BCG administration could induce innate training, identify the cell type involved, and determine whether innate training promoted resistance to bovine respiratory syncytial virus (BRSV) infection, a major cause of bovine respiratory disease in preweaned calves. A total of 24 calves were enrolled at 1–3 d of age and blocked by age into two treatment groups (BCG, n = 12; control, n = 12). BCG was given s.c. to preweaned calves. The control calves received PBS. We observed a trained phenotype, demonstrated by enhanced cytokine production in response to in vitro stimulation with LPS (TLR-4 agonist) in PBMCs and CD14+ monocytes from the BCG group 2 wk (IL-1β, p = 0.002) and 4 wk (IL-1β, p = 0.005; IL-6, p = 0.013) after BCG administration, respectively. Calves were experimentally infected via aerosol inoculation with BRSV strain 375 at 5 wk after BCG administration and necropsied on day 8 postinfection. There were no differences in disease manifestation between the treatment groups. Restimulation of bronchoalveolar lavage fluid cells isolated on day 8 after BRSV infection revealed enhanced IL-1β (p = 0.014) and IL-6 (p = 0.010) production by the BCG group compared with controls. In conclusion, results from our study show that s.c. administration of the BCG vaccine can induce trained immunity in bovine monocytes and influence cytokine production in the lung environment after BRSV infection.
Publisher
The American Association of Immunologists
Subject
Immunology and Allergy,General Medicine,Immunology
Reference37 articles.
1. United States Department of Agriculture
. 2021. Morbidity and mortality in U.S. preweaned dairy heifer calves: NAHMS dairy 2014 study calf component. Available at: https://www.aphis.usda.gov/animal_health/nahms/dairy/downloads/dairy17/morb-mort-us-prewean-dairy-heifer-nahms-2014.pdf.
2. United States Department of Agriculture, Animal and Plant Health Inspection Service
. 2008. Antibiotic use on U.S. dairy operations, 2002 and 2007. Available at: https://www.aphis.usda.gov/animal_health/nahms/dairy/downloads/dairy07/Dairy07_is_AntibioticUse_1.pdf.
3. Innate immunomodulation in food animals: evidence for trained immunity?;Byrne;Front. Immunol.,2020
4. Trained immunity: a memory for innate host defense;Netea;Cell Host Microbe,2011
5. Evidence for macrophage-mediated protection against lethal Candida albicans infection;Bistoni;Infect. Immun.,1986