Nav: Home

Pain and gain: Skin nerves anticipate and fight infection, Pitt research finds

July 25, 2019

PITTSBURGH, July 25, 2019 - Pinch yourself. If you feel pain, it's thanks to specialized nerve endings in the skin. And, in a surprising discovery, researchers at the University of Pittsburgh School of Medicine demonstrated that pain-sensing nerves also help fight skin infections and prevent its spread, suggesting a new type of immunity. The findings, based on studies in mice, were published today in the journal Cell.

"These pain sensing nerves can detect pathogens, and for the first time, we've shown that they activate an immune response and also signal protective immunity in sites adjacent to the infection," said Daniel Kaplan, M.D., Ph.D., professor of dermatology and immunology at Pitt's School of Medicine and the senior author of the study. "This demonstrates that the immune and nervous systems work synergistically for host defense. These findings also could have important implications for developing more specific therapies for autoimmune skin diseases like psoriasis."

Until about a decade ago, pain was thought to have evolved as a way for your body to tell you to stay away from a particular stimulus or to signal a problem with its function, like an injury. More recently however, researchers have shown that it may play an important role in immunity against some pathogens.

In the study, Kaplan and first author Jonathan Cohen, an M.D./Ph.D. student in Kaplan's lab, collaborated with Pitt neurobiology professors and pain experts Kathy Albers, Ph.D., and Brian Davis, Ph.D., to develop an optogenetic mouse model where pain sensing neurons in the skin could be activated by shining blue light.

They first showed that just activating these neurons released a small protein called CGRP, which recruited different types of immune cells to the site. This suggested that neurons detecting skin pathogens on their own kickstart an immune response even before sentry immune cells could.

Then in the same mouse model, they infected the animals with either Candida albicans, a fungus that causes candidiasis, commonly known as thrush, or Staphylococcs aureus, a common bacterium that can turn deadly under certain conditions.

Using optogenetics and chemical nerve blockers, the researchers showed through a series of elegant experiments that when the fungus infected the skin at one location, the nerves not only detected and initiated an immune response to fight the infection, but also sent a signal toward the spinal cord. Those signals then boomeranged back to skin at areas around the infection to activate immune defenses in anticipation, thereby preventing the infection from spreading.

The researchers called this new nerve-driven protective mechanism "anticipatory immunity."

"The advantage of involving the nervous system is that it can communicate information across a space in a span of milliseconds, compared to hours or days for the immune cells to do the same function," said Jonathan Cohen, an M.D./Ph.D. student in Kaplan's lab and the first author of the study. "It's the difference between sending Paul Revere to warn of the British advance and sending a telegram to do the same."

Kaplan says that while it remains to be seen how the findings translate to humans, they have interesting implications for autoimmune diseases of barrier tissues like the skin or gut.

"Understanding this really new type of immunity raises the intriguing question of whether we could develop a drug to selectively suppress excessive autoimmune inflammation in specific tissues, avoiding the negative side effects that come with using a broad immunosuppressant that affects the entire body," he says.

Additional authors on the study included Tara N. Edwards, Ph.D., Andrew W. Liu, Toshiro Hirai, Ph.D., Marsha Ritter Jones, M.D., Ph.D., Yao Li, Ph.D., Shiqun Zhang, Ph.D., Jonhan Ho, M.D., Brian M. Davis, Ph.D., and Kathryn M. Albers, Ph.D., all of Pitt; and Jianing Wu of Tsinghua University in China.
-end-
The study was supported by National Institutes of Health grants 1S10OD011925-01, T32AI060525, R01AR071720 and a grant from Pitt's Department of Anesthesiology and Perioperative Medicine.

To read this release online or share it, visit http://www.upmc.com/media/news/072519-kaplan-cell-anticipatory-immunity.

About the University of Pittsburgh Schools of the Health Sciences The University of Pittsburgh Schools of the Health Sciences include the schools of Medicine, Nursing, Dental Medicine, Pharmacy, Health and Rehabilitation Sciences and the Graduate School of Public Health. The schools serve as the academic partner to the UPMC (University of Pittsburgh Medical Center). Together, their combined mission is to train tomorrow's health care specialists and biomedical scientists, engage in groundbreaking research that will advance understanding of the causes and treatments of disease and participate in the delivery of outstanding patient care. Since 1998, Pitt and its affiliated university faculty have ranked among the top 10 educational institutions in grant support from the National Institutes of Health. For additional information about the Schools of the Health Sciences, please visit http://www.health.pitt.edu.

http://www.upmc.com/media

Contact: Arvind Suresh
Office: 412-647-9966
Mobile: 412-509-8207
E-mail: SureshA2@upmc.edu

Contact: Gloria Kreps
Office: 412-586-9764
Mobile: 412-417-2582
E-mail: KrepsGA@upmc.edu

University of Pittsburgh

Related Immune Response Articles:

Discovering the early age immune response in foals
Researchers at the Cornell University College of Veterinary Medicine have discovered a new method to measure tiny amounts of antibodies in foals, a finding described in the May 16 issue of PLOS ONE.
Nixing the cells that nix immune response against cancer
For first time, study characterizes uptick of myeloid-derived suppressor cells in the spleens of human cancer patients, paving the way for therapies directed against these cells that collude with cancer.
Jumbled chromosomes may dampen the immune response to tumors
How well a tumor responds to immunotherapy may depend in part on whether its chromosomes are intact or in a state of disarray, a new study reports.
Tailored organoid may help unravel immune response mystery
Cornell and Weill Cornell Medicine researchers report on the use of biomaterials-based organoids in an attempt to reproduce immune-system events and gain a better understanding of B cells.
Tweaking the immune response might be a key to combat neurodegeneration
Patients with Alzheimer's or other neurodegenerative diseases progressively loose neurons yet cannot build new ones.
Estrogen signaling impacted immune response in cancer
New research from The Wistar Institute showed that estrogen signaling was responsible for immunosuppressive effects in the tumor microenvironment across cancer types.
No platelets, no immune response
When a virus attacks our organism, an inflammation appears on the affected area.
Malaria: A genetically attenuated parasite induces an immune response
With nearly 3.2 billion people currently at risk of contracting malaria, scientists from the Institut Pasteur, the CNRS and Inserm have experimentally developed a live, genetically attenuated vaccine for Plasmodium, the parasite responsible for the disease.
New finding will help target MS immune response
Researchers have made another important step in the progress towards being able to block the development of multiple sclerosis and other autoimmune diseases.
Flu infection reveals many paths to immune response
A new study of influenza infection in an animal model broadens understanding of how the immune system responds to flu virus, showing that the process is more dynamic than usually described, engaging a broader array of biological pathways.

Related Immune Response Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...