Anti-Inflammatory Properties of Fructo-Oligosaccharides in a Calf Lung Infection Model and in Mannheimia haemolytica-Infected Airway Epithelial Cells

Yang Cai,Saskia Braber,Myrthe S. Gilbert,Gert Folkerts,Walter J. J. Gerrits

doi:10.3390/nu13103514

Abstract

Emerging antimicrobial-resistant pathogens highlight the importance of developing novel interventions. Here, we investigated the anti-inflammatory properties of Fructo-oligosaccharides (FOS) in calf lung infections and in airway epithelial cells stimulated with pathogens, and/or bacterial components. During a natural exposure, 100 male calves were fed milk replacer with or without FOS for 8 weeks. Then, immune parameters and cytokine/chemokine levels in the bronchoalveolar lavage fluid (BALF) and blood were measured, and clinical scores were investigated. Calf primary bronchial epithelial cells (PBECs) and human airway epithelial cells (A549) were treated with Mannheimia haemolytica, lipopolysaccharides (LPS), and/or flagellin, with or without FOS pretreatment. Thereafter, the cytokine/chemokine levels and epithelial barrier function were examined. Relative to the control (naturally occurring lung infections), FOS-fed calves had greater macrophage numbers in BALF and lower interleukin (IL)-8, IL-6, and IL-1β concentrations in the BALF and blood. However, FOS did not affect the clinical scores. At slaughter, FOS-fed calves had a lower severity of lung lesions compared to the control. Ex vivo, FOS prevented M. haemolytica-induced epithelial barrier dysfunction. Moreover, FOS reduced M. haemolytica- and flagellin-induced (but not LPS-induced) IL-8, TNF-α, and IL-6 release in PBECs and A549 cells. Overall, FOS had anti-inflammatory properties during the natural incidence of lung infections but had no effects on clinical symptoms.

Highlights

Due to the possible presence of FOS in the systemic circulation after oral administration, we investigated whether FOS could affect the signaling of TLR4 and 5 and the subsequent inflammatory response in primary bronchial epithelial cells (PBECs), as well as whether they could restore the impaired epithelial barrier function induced by M. haemolytica
This study investigated whether FOS could reduce lung infection and subsequ ica-stimulated PBECs were used to investigate the anti-inflammatory properties of FOS
We showed that FOS have the ability to inhibit the levels of these cytokines in vitro and in vivo, thereby protecting the integrity of the epithelial barrier, as observed by a higher Transepithelial Electrical Resistance (TEER) value and the expression of tight/adherens junction proteins, and the lower lucifer yellow flux in PBECs

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Lung infections are a common destructive public health problem in both humans and livestock, associated with high morbidity, mortality, and costs [1,2,3]. When the defense of the respiratory system is impaired, pathogens quickly invade and colonize the epithelium of the lower respiratory tract, resulting in the development of lung infections [2]. Antibiotics are the main treatment for lung infections, but the emergence of bacterial resistance necessitates more extensive research on strategies to improve (lung) health, and reduce the use of antibiotics

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