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 describes this newly discovered mechanism in a report published 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. "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."
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, the 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.
https://www.masseyeandear.org/news/press-releases/2018/11/exosomes-swarm-to-protect-against-bacteria-inhaled
https://www.jacionline.org/article/S0091-6749(18)31351-4/fulltext
Latest News
Protein that helps COVID-19…
By newseditor
Posted 26 Jul
Spinal Muscular Atrophy (SM…
By newseditor
Posted 26 Jul
Link between bowel movement…
By newseditor
Posted 26 Jul
Inhibition of IL-11 signall…
By newseditor
Posted 25 Jul
Brain changes linked to obe…
By newseditor
Posted 25 Jul
Other Top Stories
Selective promiscuity in the binding of E. coli Hsp70 to an unfolde…
Read more
Spaceflight wreaks havoc on liver metabolism
Read more
How hyaluronic acid shape the organs
Read more
How do our organs know when to stop growing?
Read more
New mechanism for protecting DNA identified!
Read more
Protocols
A systems biology approach…
By newseditor
Posted 24 Jul
quantms: a cloud-based pipe…
By newseditor
Posted 22 Jul
Emerging tools and best pra…
By newseditor
Posted 19 Jul
Directly selecting cell-typ…
By newseditor
Posted 17 Jul
PUFFFIN: an ultra-bright, c…
By newseditor
Posted 16 Jul
Publications
Hepatocyte-intrinsic SMN de…
By newseditor
Posted 26 Jul
Aberrant bowel movement fre…
By newseditor
Posted 26 Jul
A pseudoautosomal glycosyla…
By newseditor
Posted 26 Jul
Microglia protect against a…
By newseditor
Posted 26 Jul
Rigor and reproducibility i…
By newseditor
Posted 26 Jul
Presentations
Myelin plasticity in the ve…
By newseditor
Posted 10 Jun
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar