Exosomes ‘swarm’ to protect against bacteria inhaled through the nose

Bacteria are present in just about every breath of air we take in. How the airway protects itself from infection from these bacteria has largely remained a mystery—until now. When bacteria are inhaled, exosomes, or tiny fluid-filled sacs, are immediately secreted from cells which directly attack the bacteria and also shuttle protective antimicrobial proteins from the front of the nose to the back along the airway, protecting other cells against the bacteria before it gets too far into the body.

A research team from Massachusetts Eye and Ear describes this newly discovered mechanism in a report published online today in the Journal of Allergy and Clinical Immunology (JACI). The findings shed new light on our immune systems—and also pave the way for drug delivery techniques to be developed that harness this natural transportation process from one group of cells to another.

“Similar to kicking a hornets nest, the nose releases billions of exosomes into the mucus at the first sign bacteria, killing the bacteria and arming cells throughout the airway with a natural, potent defense” said senior author Benjamin Bleier, MD, a sinus surgeon at Massachusetts Eye and Ear and associate professor of otolaryngology at Harvard Medical School. “It’s almost like this swarm of exosomes vaccinates cells further down the airway against a microbe before they even have a chance to see it.”

The JACI study was motivated by a perplexing previous finding from Dr. Bleier’s lab a few years ago. In studies of sinus inflammation, researchers found that proteins in the cells of the nasal cavity were also present in patients’ nasal mucus. The team wanted to know why and how these proteins were moving from the cells into the nasal mucus, hypothesizing that exosomes had something to do with that process.

The new findings described in the JACI study shed light on this process. When cells at the front of the nose detect a bacterial molecule, they trigger a receptor called TLR4, which stimulates exosome release. When that happens, an innate immune response occurs within 5 minutes. First, it doubles the number of exosomes that are released into the nose. Second, within those exosomes, a protective enzyme, nitric oxide synthase, also doubles in amount. As a well-known antimicrobial molecule, nitric oxide potently arms each exosome to defend against bacteria.

The exosome “swarm” process gets an assist from another natural mechanism of the nose—mucocilliary clearance. Mucocilliary clearance sweeps the activated exosomes over to the back of the nose, along with information from cells that have already been alerted to the presence of bacteria. This process prepares the cells in the back of the nose to immediately fight off the bacteria, arming them with defensive molecules and proteins.

In their experiments described in the JACI report, Dr. Bleier’s team sampled patients’ mucus and grew up their own cells in culture. They then simulated an exposure to bacteria and measured both the number and composition of the released exosomes. They found a doubling of both the number of exosomes and of antibacterial molecules after stimulation. The team then confirmed this finding in live patients and further showed that these stimulated exosomes were as effective as antibiotics at killing the bacteria. Finally, the team showed that the exosomes were rapidly taken up by other epithelial cells, where they were able to “donate” their antimicrobial molecules.

Along with this new understanding of the innate immune system, the authors on the JACI paper suggest that their findings may have implications for new methods of delivering drugs through the airway to be developed. More specifically, as natural transporters, exosomes could be used to transfer inhaled packets of therapeutics to cells along the upper airway—and possibly even into the lower airways and lungs.

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Study finds alcohol advertising rules may fail to protect Australian kids

Regulations introduced to restrict the placement of alcohol advertising are unlikely to reduce young people’s exposure to alcohol marketing in Australia, new research led by Curtin University has found.

The research, published in the Drug and Alcohol Review journal, critically reviewed the placement rules added to the industry-run Alcohol Beverages Advertising Code (ABAC) Scheme in November 2017 and evaluated their ability to effectively regulate the placement of alcohol marketing in Australia.

Co-author Ms Julia Stafford, from the Alcohol Programs Team at the Public Health Advocacy Institute of WA (PHAIWA) based at Curtin University, said the placement rules do not meet the criteria for effective self-regulation and do not appear to have introduced any additional safeguards for young people.

“The placement rules were introduced to put some restrictions on where alcohol companies could market their products. The rules include requiring advertisers meet other industry codes that apply to the placement of alcohol advertising, market their products to audiences that are at least 75 per cent adults, and ensure alcohol advertising is not placed within programs aimed at minors,” Ms Stafford said.

“We found that they are unlikely to reduce young people’s exposure to alcohol marketing as they are very narrow in scope, exclude key forms of promotion, and place minimal restrictions on marketers. All but one of the 24 placement-related determinations published in the first six months of the placement rules were either dismissed or found to be ‘no fault’ breaches.

“The rules allow alcohol advertising to be broadcast during televised sport on weekends and public holidays, and do little to limit outdoor advertising. Alcohol ads placed in shopping centres, at sports stadiums, on public transport vehicles, and at bus stops or train stations outside of a 150m radius of a school are all consistent with the placement rules.”

First author Ms Hannah Pierce, also from the Alcohol Programs Team at PHAIWA, said the review also identified substantial flaws in the regulatory processes of the placement rules.

“The alcohol and advertising industries were heavily involved in the development of the rules, but there was no evidence of consultation with other stakeholders. There are also no penalties for marketers who breach the rules,” Ms Pierce said.

“Our findings support existing evidence that industry-managed systems fail to effectively regulate alcohol marketing and government intervention is needed if young people’s wellbeing is to be a priority.

“It has now been 12 months since the placement rules were introduced and our research shows that a comprehensive, independent review of the ABAC Scheme is needed.”

The research was also co-authored by researchers from the Public Health Advocacy Institute of WA and the School of Psychology at Curtin University and Cancer Council WA.

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Health Tip: Use Petroleum Jelly to Protect Your Skin

— The skin is the largest organ in the human body. And petroleum jelly is an inexpensive, readily available way to help protect it.

The American Academy of Dermatology suggests:

  • Apply petroleum jelly to damp skin, including lips and eyelids.
  • Apply it to minor cuts, scrapes and scratches to keep nearby skin from drying out.
  • Apply it to body areas prone to chafing.
  • Apply it after a diaper change if your child is prone to a rash.
  • Apply it to nails and cuticles between polishes. This will minimize brittleness and help prevent chipping.

Posted: November 2018

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