Acute and repetitive inhalational organic dust exposure modulates immune response mitigation by omega-3 fatty acids and susceptibility to secondary respiratory bacterial infection

Abstract

Inhalational organic dust exposure (ODE), both acute and repetitive, is inflammatory and highly neutrophilic. Prolonged ODE is clinically linked to an increased risk of asthma and COPD development, to both workers in the livestock and agricultural industries, as well as individuals who live in proximity to such operations. As such, a greater understanding of the immune response to ODE, increased focus on therapeutic strategies, and understanding of translational insights into comorbid infections is necessary. This work provides key insights into a pivotal process implicated in furthering inflammation, neutrophil extracellular trap (NET) formation in acute dust exposure. Furthermore, insights into the chronic inflammatory environment crafted by repetitive ODE are investigated and compared to a mouse model of balanced omega-3 fatty acids, key resolution promoting parent molecules. Finally, this work utilizes a mouse model of repetitive ODE to investigate if the inflammatory environment promotes susceptibility to the common respiratory bacterium, Streptococcus pneumoniae. Collectively, this work provides key insights into immune cell population alterations in murine models of acute and repetitive ODE. I demonstrate that NET formation is increased in acute ODE in a subset of mature and lung-resident neutrophil populations, that repetitive ODE in a mouse model of balanced omega-3 fatty acids preferentially recruits monocyte populations in a sex dependent manner to the airway and lung tissue, and that repetitive ODE is protective against secondary S. pneumoniae infection and mortality through the induction of effector and highly cytotoxic lymphocyte populations.