When Noses Counterattack

Each breath we take gives bacteria the opportunity to infiltrate our airways. Fortunately, our noses have their own effective mechanisms of defense. Researchers at Massachusetts Eye and Ear claim to have observed, for the first time, cells in the front of the nose detecting pathogenic bacteria in the nasal cavity. In response to bacteria, the cells release swarms of exosomes into the nasal mucus to attack invading microbes. “This is one of the only examples where the immune system actually extends outside the body (in this case into the airway) to fight off bacteria,” says Benjamin Bleier, Associate Professor of Otolaryngology at Massachusetts Eye and Ear and senior author of a new study (1). “The detection of lipopolysaccharide molecular signatures in pathogenic bacteria triggers increased numbers of exosomes, packaged with antimicrobial molecules, to be released.”

The exosomes employ a two-prong approach to defense: attacking bacteria directly with potency equivalent to antibiotics, and donating their antimicrobial proteins to epithelial cells by moving to the back of the nose through the natural mucus blanket where they are absorbed.

“The idea for this research came from our previous studies looking into the causes of chronic rhinosinusitis. We discovered that exosomes were secreted into the nasal mucus and were able to transport pro-inflammatory proteins between cells. However, in our healthy control patients, we also saw billions of exosomes being secreted, which led us to question what their role was in the normal healthy nose,” explains Bleier. Though research at the time had explored the role of exosomes in gut cell cultures, no such information existed in regard to the nose.

Exosomes transport proteins between nasal epithelial cells on time scales that outpace mucociliary clearance (the movement of cilia on mucosal respiratory surfaces). According to Bleier, the efficiency of drug uptake via the nose could be improved if therapeutics were designed to mimic exosomes. However, as the composition of exosomes is similar to their host cells, they would likely trigger an immune response when introduced to a new host. Therefore, novel exosome-based therapeutics would need to allow rapid cellular uptake to occur, without eliciting an immune response.

“As exosomes are ubiquitous within the body, it is highly likely that they have a similar role in other organ systems too,” adds Bleier. “Recent studies have also highlighted the cross-talk between the immune system and the human microbiome, so exosomes may also be responsible for maintaining a healthy commensal community in the nose by targeting pathogenic bacteria and tolerating healthy microbes.”

Bleier and his team now plan to conduct large-scale bioinformatic studies to correlate the exosome proteome to the nasal microbiome, which could also have implications in understanding and treating chronic infectious and inflammatory disorders of the nose and sinuses.