Fusobacterium nucleatum infection modulates the transcriptome and epigenome of HCT116 colorectal cancer cells in an oxygen-dependent manner.

Fusobacterium nucleatum, a gram-negative oral bacterium, has been consistently validated as a strong contributor to the progression of several types of cancer, including colorectal (CRC) and pancreatic cancer. While previous in vitro studies have shown that intracellular F. nucleatum enhances malignant phenotypes such as cell migration, the dependence of this regulation on features of the tumor microenvironment (TME) such as oxygen levels are wholly uncharacterized. Here we examine the influence of hypoxia in facilitating F. nucleatum invasion and its effects on host responses focusing on changes in the global epigenome and transcriptome. Using a multiomic approach, we analyze epigenomic alterations of H3K27ac and global transcriptomic alterations sustained within a hypoxia and normoxia conditioned CRC cell line HCT116 at 24 h following initial infection with F. nucleatum. Our findings reveal that intracellular F. nucleatum activates signaling pathways and biological processes in host cells similar to those induced upon hypoxia conditioning in the absence of infection. Furthermore, we show that a hypoxic TME favors F. nucleatum invasion and persistence and therefore infection under hypoxia may amplify malignant transformation by exacerbating the effects induced by hypoxia alone. These results motivate future studies to investigate host-microbe interactions in tumor tissue relevant conditions that more accurately define parameters for targeted cancer therapies.

Nanoparticle-neutrophils interactions for autoimmune regulation.

Neutrophils play an essential role as 'first responders' in the immune response, necessitating many immune-modulating capabilities. Chronic, unresolved inflammation is heavily implicated in the progression and tissue-degrading effects of autoimmune disease. Neutrophils modulate disease pathogenesis by interacting with the inflammatory and autoreactive cells through effector functions, including signaling, degranulation, and neutrophil extracellular traps (NETs) release. Since the current gold standard systemic glucocorticoid administration has many drawbacks and side effects, targeting neutrophils in autoimmunity provides a new approach to developing therapeutics. Nanoparticles enable targeting of specific cell types and controlled release of a loaded drug cargo. Thus, leveraging nanoparticle properties and interactions with neutrophils provides an exciting new direction toward novel therapies for autoimmune diseases. Additionally, recent work has utilized neutrophil properties to design novel targeted particles for delivery into previously inaccessible areas. Here, we outline nanoparticle-based strategies to modulate neutrophil activity in autoimmunity, including various nanoparticle formulations and neutrophil-derived targeting.