Microorganisms and their components present in livestock ambient air in relation to respiratory symptoms

Abstract

Exposure to livestock farm BioPM has been shown to have a range of effects to promote or inhibit different facets of allergic respiratory diseases. The main aim of this thesis was to investigate whether microorganism or their components present in indoor ambient air of livestock farms contribute to the initiation and/or worsening of respiratory symptoms in asthmatic patients.

In Chapter 2, we characterized the microbial profiles of livestock farms BioPM and their effect on innate receptors and on the cytokine production by monocytic cells. The bacterial and fungal communities from livestock airborne BioPM were found to be grouped according to animal farm. BioPM derived from all farms contained mainly ligands for TLR2 and TLR4, only the pig farm BioPM activated TLR5. BioPM from all farms induced a concentration-dependent increase in IL-6 production by monocytes, which was mainly dependent on TLR4 activation.

Chapter 3 describes BioPM-induced oxidative stress (OS) and inflammation when using PBMCs from healthy individuals and asthmatic patients before and during loss of disease control. BioPM from all farms induced the enhancement of an inflammatory response (IL-1β, IL-10, TNFα and IFNγ), which were abrogated by pre-treatment with the antioxidant NAC, indicative of a mechanism (partly) related to oxidative stress. However, we found no marked differences in OS and inflammatory response to BioPM between PBMCs from healthy controls and asthmatic patients.

Chapter 4 shows how BioPM from chicken and pig farms could modify airway allergic responses by using an OVA-induced experimental mouse model. The differences between farms were also described. All farm BioPM elicited a neutrophil influx in BALF of non-allergic mice. BioPM derived from pig farm 2 induced the highest inflammatory cellularity in BALF in allergic mice than BioPM from other farms. BioPM from all farms elicited Th17 cytokine (IL-23) production except BioPM from chicken farm 2, which induced an increase of Th2 cytokine (IL-5). These results indicate that inhalation exposure of BioPM from chicken and pig farms may result in enhancement of airway allergic response in mice following exposure to OVA that involves Th17 and Th2 responses. The different effects among the farms may be associated with the differences in airborne microbiomes composition reported in Chapter 2.

We studied further the effect of goat farms BioPM on airway allergic response using the airway allergic murine model and described the possible underlying mechanisms in Chapter 5. Neutrophilic and eosinophilic responses were enhanced in non-allergic and allergic mice after exposure to goat farm BioPM, indicating enhanced airway allergic inflammation in both saline and OVA-challenged mice. RNAseq analysis of lungs from mice exposed to BioPM indicate that neutrophil chemotaxis and oxidation-reduction processes were the most apparent genomic pathways in non-allergic and allergic mice, respectively.