Impact of extracellular vesicles derived from Staphylococcus aureus Newbould 305 on innate immune response of mice mammary gland

Abstract

Mastitis, an inflammation of the mammary gland, is the most prevalent production disease in dairy herds worldwide. It affects animal health and milk quality and causing huge economic losses. Staphylococcus aureus is one of the most important etiological agents of mastitis, and treatment against S. aureus-induced mastitis is still ineffective. Although S. aureus is extensively studied, the mechanisms involved in its pathogenicity are not yet fully understood. Since secretory factors are important components in S. aureus pathogenesis, the role of extracellular vesicles (EVs) in infections is an emerging field of research in S. aureus. EVs are indeed nano-sized biological particles ranging from 30 to 150 nm and that are actively secreted into the surrounding environment by any living cell. They play a crucial role in intercellular communication and vectorization of bioactive molecules, and can modulate the metabolism and physiology of target cells, participating in pathogenesis, modulation of the immune response and exchange of material. Various virulence factors have been identified in S. aureus EVs. Additionally, EVs secreted by S. aureus N305 strain, a bovine mastitis isolate, induced the expression of IL-8 in vitro, and promoted tissue inflammation, deterioration, and local cytokine production, in vivo, suggesting a role of EVs in mastitis pathogenesis. The objective of this work is to investigate the involvement of S. aureus EVs in the host-pathogen interactions at the cellular and molecular levels, with special attention to the modulation of cellular and immune response. For that, an RNA-seq approach was chosen to identify eukaryotic genes and signaling pathways targeted and triggered by S. aureus N305 EVs in vitro, which is ongoing. Afterwards, the expression of relevant genes activated in vitro will be measured in mammary gland tissues exposed to EVs to confirm the mechanisms of action of EVs in vivo. This work will improve our knowledge on the interactions of EVs with host cells, bringing information about S. aureus mastitis pathogenesis. Additionally, it will also provide molecular and functional data for the use of EVs as biotechnological agents, e.g. for the development of vaccines or drugs for mastitis prevention