Journal Article

Aerosol vaccination with Bacille Calmette-Guerin induces a trained innate immune phenotype in calves

Vang, Dua X., Guerra-Maupome, Mariana, McGill, Jodi L.

2019

Overview

Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is a live attenuated vaccine for use against tuberculosis (TB); however, it is known to reduce childhood mortality from infections other than TB. The unspecific protection induced by BCG vaccination has been associated with the induction of memory-like traits of the innate immune system identified as 'trained' immunity. In humans and mouse models, in vitro and in vivo BCG training leads to enhanced production of monocyte-derived proinflammatory cytokines in response to secondary unrelated bacterial and fungal pathogens. While BCG has been studied extensively for its ability to induce innate training in humans and mouse models, BCG's nonspecific protective effects have not been defined in agricultural species. Here, we show that in vitro BCG training induces a functional change in bovine monocytes, characterized by increased transcription of proinflammatory cytokines upon restimulation with the toll-like receptor agonists. Importantly, in vivo, aerosol BCG vaccination in young calves also induced a 'trained' phenotype in circulating peripheral blood mononuclear cells (PBMCs), that lead to a significantly enhanced TLR-induced proinflammatory cytokine response and changes in cellular metabolism compared to PBMCs from unvaccinated control calves. Similar to the long-term training effects of BCG reported in humans, our results suggest that in young calves, the effects of BCG induced innate training can last for at least 3 months in circulating immune populations. Interestingly, however, aerosol BCG vaccination did not 'train' the innate immune response at the mucosal level, as alveolar macrophages from aerosol BCG vaccinated calves did not mount an enhanced inflammatory response to secondary stimulation, compared to cells isolated from control calves. Together, our results suggest that, like mice and humans, the innate immune system of calves can be 'trained'; and that BCG vaccination could be used as an immunomodulatory strategy to reduce disease burden in juvenile food animals before the adaptive immune system has fully matured.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adaptive systems / Aerosols / Alveoli / Analgesics / Animal models / Animals / Antitubercular agents / Bacillus Calmette-Guerin vaccine / BCG / Biology and Life Sciences / Blood circulation / Calves / Cattle / Children / Containers / Cytokines / Cytokines - immunology / Disease / EDTA / Female / Gene expression / Health aspects / Humans / Immune response / Immune system / Immunity / Immunity, Innate / Immunity, Mucosal / Immunological memory / Immunomodulation / Infection / Infections / Inflammation / Inflammatory response / Innate immunity / Laboratory rats / Leukocytes (mononuclear) / Macrophages / Macrophages, Alveolar - immunology / Male / Medicine and Health Sciences / Metabolism / Mice / Monocytes / Mucosal immunity / Mycobacterium bovis - immunology / Pathogenic microorganisms / Peripheral blood mononuclear cells / Phenotypes / Physical Sciences / Pneumonia / Proteins / Respiratory diseases / Respiratory syncytial virus / Studies / Toll-like receptors / Toll-Like Receptors - immunology / Training / Transcription / Tropical diseases / Tuberculosis / Tuberculosis vaccines / Tuberculosis Vaccines - immunology / Tuberculosis Vaccines - pharmacology / Tuberculosis, Bovine - immunology / Tuberculosis, Bovine - prevention & control / Vaccination / Vaccines / Veterinary medicine