Abstract

In today’s environmentally conscious climate, recycling and reusing essential elements is of upmost importance to preserve our delicate ecosystem. This same mantra can be examined in terms of hostpathogen relationships in chronic respiratory disease. Cystic Fibrosis is a disease characterized for years in terms of defective mucociliary clearance of lung mucus and pathogens leading to a cycle of chronic respiratory infections obtained from the environment. Today, we know that innate immune defects also contribute to the heavy burden of respiratory infection in CF. However, when it comes to host-pathogen interactions in CF, autophagy-mediated recycling of essential proteins has gone awry. Autophagy is a conserved, physiologic process whereby host cells degrade cytoplasmic material via lysosomes. Autophagy functions can range from recycling of large organelles and molecules to clearance of intracellular pathogens [1]. Triggers of autophagy are varied, including starvation, stress, infection, and immune signaling among others. Over the last few years, several groups have demonstrated defects in autophagy in relation to CF, including Cystic Fibrosis Transmembrane Regulator (CFTR) associated sequestration of essential autophagy molecules [2,3] and inflammatory signaling related to defective autophagy [4]. Without proper autophagy recycling of proteins, essential autophagy molecules such as Beclin-1 accumulate in aggresomes, rendering subsequent autophagy interactions ineffective. Additionally, recent studies in CF have demonstrated defects in bacterial clearance of Burkholderia cenocepacia [5] and Pseudomonas aeruginosa [6] due to defective autophagy. Without essential autophagy flux, patients with CF are unable to mount effective autophagy-mediated responses against specific pathogens, but it is unknown if this affects all pathogen interactions in CF. Immunomodulation in CF is a difficult task considering the polymicrobial milieu that most patients possess. However, innate immune responses must be considered seriously in the face of a global

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