Innate Immunity: The body’s first response to microbial challenges.

Innate immunity in the context of COVID-19  

 Mammals have complex immune systems.  Survival depends on the ability to integrate and coordinate adaptive and innate responses to microbial threats.  Adaptive immune responses take days to weeks to produce antibodies to new bacteria and viruses.  In the mean time, the body has to fight off the infection.  Innate immunity is that first line of defense.  Also, it is the entire defense against a novel pathogen before the slower adaptive immune system has an opportunity to respond. This is the reality and challenge that we face in COVID-19.

Humans have multiple layers of innate protection.  Skin on the outside of the body and mucosal epithelial cells, like those found in the respiratory and digestve tracts, provide barrier protection.  Many cell types are sensitive to the presence of microbes, providing cellular surveillance and communications between cells found at mucosal surfaces with other parts of the immune system.  As part of this system of defense, virtually all metazoan animals, including humans, release antimicrobial peptides (AMPs) that both kill invading microbes and act as immune signaling mediators.  Most immune communications are complex but subtle. Under optimal conditions, regulators of immune responses maintain balanced responses, neither too strong nor too weak. An example of an immune system regulator is vitamin D.  Many people world wide are vitamin D deficient.  Without adequate vitamin D, the body’s immune system cannot maintain optimal balance to protect against microbes.

Because of innate immunity, most microbes are not dangerous to other life forms, including humans.  The antimicrobial peptides, AMPs that we mention above,  are key element in successfully maintaining boundaries between the mammalian host and the ever present microbial flora to which all life forms are exposed.   An example of antimicrobial innate protection is cathelicidin and a smaller fragment of it  known as LL37. LL37 is a broad-spectrum antibacterial and antiviral AMP best known for its role in protecting against the organism that causes tuberculosis. Interestingly, LL37 can also destroy envelope viruses, similar to the virus that causes COVID-19.

Our publication in Frontiers in Public Health tells more of the story.  We explain how Vitamin D regulates the production of LL37 and how carbon particles in air pollution can interfere.

This post is an adapted excerpt from our recent paper published in Frontiers in Public Health. Download the full article freely here: https://www.frontiersin.org/articles/10.3389/fpubh.2020.00232/full 

Citation: Crane-Godreau MA, Clem KJ, Payne P and Fiering S (2020) Vitamin D Deficiency and Air Pollution Exacerbate COVID-19 Through Suppression of Antiviral Peptide LL37. Front. Public Health 8:232. doi: 10.3389/fpubh.2020.00232

Keywords: COVID-19, Vitamin D deficiency, cathelicidin/LL37, air pollution, citrullination of peptide, carbon nanoparticles, African American, tobacco smoke

 

FOR IMMEDIATE RELEASE- COVID RELATED

FOR IMMEDIATE RELEASE                                                                                                                                                     Update 6 June, 2020

Contact:                                                                                                                                                                                      Mardi Crane-Godreau, PhD                                                                                                                                                   EMAIL: mardi.dartmouth.related@gmail.com

 

 Innate immune protection against COVID-19 is compromised by vitamin D deficiency & air pollution.

 

Protection against COVID-19 requires both adequate vitamin D and clean air. 

Absence of LL37, a naturally occurring anti-viral secretion of the human respiratory tract, may explain serious vs. mild COVID-19 symptoms.  Production of LL37 is regulated by Vitamin D. Individuals with vitamin D deficiency may not produce adequate LL37 to protect against the COVID-19 or other viral infections.

LL37 destroys envelope viruses by damaging their envelope. This happens by virtue of its positive electrical charge.  When fine particles in air pollution come in contact with LL37, they neutralize the positive charge of LL37, leaving LL37 inert. This leaves viruses to reproduce and spread freely.  Consistent with observations of high death rates and high levels of pollution in COVID-19 hot spots, the neutralization of LL37 by nanoparticles may explain these phenomena.

Protection against COVID-19 requires both adequate vitamin D and clean air.  Interestingly, the absence of either or both, has adverse impact on the ability to fight any viral infection.  Since LL37 also modulates immune responses, its absence not only leaves those with viral infections vulnerable to direct viral damage but also to inflammatory responses by the immune system.

Crane-Godreau, Clem, Payne and Fiering, a team of Dartmouth scientists, published their insights in Frontiers in Public Health.  https://www.frontiersin.org/articles/10.3389/fpubh.2020.00232/full

Dr. Crane-Godreau, explained, “Our innate immune system is the first line of defense against infection and the only line of defense when the body is challenged by a novel microbe. It takes days to weeks to develop antibodies, but in the mean time, you have to survive the infection.  LL37 plays a critical role in protecting against both viral and bacterial infections. The body requires adequate vitamin D to regulate its production.  This is consistent with reports by scientist and doctors, that vitamin D is playing a role in reducing the impact of the virus.”

Crane-Godreau commented, “Early in the pandemic, while we felt that LL37 was likely protecting populations with adequate vitamin D levels, we were perplexed by the high death rates in various high pollution hot spots.  Further investigation led to our understanding that LL37 can be neutralized by coming in contact with carbon nanoparticles. Those are the fine particles found in industrial and transportation associated air pollution. Risk exists from other sources of air pollution including wood burning stoves and primary and second-hand smoke. ”

Emergency medicine clinician and co-author, Dr. Kathleen Clem, pointed to the link between adequate vitamin D levels and better outcomes in patients who contract COVID-19. She added “Air quality is also a factor. While mask-wearing decreases spread of the virus, the correct types of masks can also protect against poor air quality. We see both clean air and adequate vitamin D levels as necessary to minimize illness and deaths from COVID-19.”

LL37 has demonstrated antiviral activity against several other envelope viruses including Respiratory Syncytial Virus, Influenza A, Hepatitis C, Dengue Virus, HIV-1 and Vaccinia Virus.  It does this by destroying the envelope with its positive charge.

The paper calls for development of relevant protocols for prevention and treatment of COVID-19.  The authors also call for mitigation of exposure to fine particles from industrial and transportation associated air pollution as well as from primary and second-hand tobacco smoke and other domestic sources.

COVID- figure -diagram w legend

Vitamin D: What’s all the fuss?

Mardi Crane-Godreau, PhD

Vitamin D, what’s all the fuss?  Is it relevant to COVID-19? To read about new developments, click here.  But if you simply want to understand a little more about this fascinating hormone/vitamin, read on.

Vitamins are needed in small quantities to support normal life processes. Most can be obtained from food sources.   However, since diets vary, some need to be obtained from supplements.  Vitamin D is somewhat of a special case.  It’s actually a hormone, obtained from food or supplements, but also made by the body under favorable conditions.  We humans are able to make our own vitamin D when our skin is exposed to sunlight.  Exposing arms and legs for about 10 to 15 minutes per day, when the sun is at least halfway up from the horizon, can go a long way to provide what is needed by the body to make vitamin D.

A note of caution! Sunburn is dangerous and extended time in the sun does not mean that your body will make more vitamin D.   Our systems have a natural shut off mechanism.  After a certain point, the body stops making vitamin D, so this is one of those instances where too much can be worse than not enough.

In this time of COVID-19, many articles have been written about the possible benefits of vitamin D in reducing the impact of the disease.   Some have looked at evidence from patient records comparing their previously measured vitamin D levels with how sick they became with COVID-19.   Others have looked at established information about which groups of people tend to have adequate vitamin D levels and which groups tend to have low, deficient levels of vitamin D.   Many of these articles point to evidence that vitamin D has a protective benefit when fighting respiratory viral infections in general.  They also point to recent evidence that COVID-19 is less severe when vitamin D levels are adequate.

Sunlight to Vit D

As a hormone, vitamin D has a wide range of effects on the body.  It helps to regulate over a thousand genes, many of which are related to the immune system.  Vitamin D modulates immune responses allowing for a balanced response by the body to challenges from bacteria and viruses.  It plays a key role in making molecules that attack and destroy microbes.  It also supports cell to cell signaling, making it possible for the immune system to respond without excesses that can be as dangerous as the microbes.

How do you know if you are getting enough vitamin D?  Simple blood tests are available to determine if your level is sufficient to meet the needs of your body. Vitamin D deficiency and insufficiency are found widely in industrialized societies world wide, especially in areas more than 37 degrees latitude distant from the equator.   Deficiency is also common in older adults, in individuals with diabetes, heart disease, obesity, hypertension and some forms of cancer.  In the US,  vitamin D deficiency is documented to be common in those with African American genetic heritage.  Vitamin D deficiency is defined as having a level of 25-hydroxyvitamin D below 20 ng/ml (50 nmol/liter).  When vitamin D is between 21–29 ng/ml (52.5–72.5 nmol/liter) it is defined as insufficient.  If available, ask your medical provider for a test.

Sources differ on how much vitamin D individuals should take.  In 2011, The Endocrine Society, a prestigious group of professional endocrinologists who treat patients with hormonal disorders, recommends from 1,500 iu  (37.5 mcg) to 2,000 iu (50 mcg) for anyone over 19 years old to raise the blood level of 25(OH)D consistently above 30 ng/ml (75 nmol/liter).    For those 19 and under, they suggest that at least 1000 IU/d of vitamin D may be required to achieve and maintain a level consistently above 30 ng/ml (75 nmol/liter). They acknowledge that specific at-risk groups may need higher levels of vitamin D supplementation to achieve and maintain sufficient vitamin D.  The Endocrines Society also states that a maximum safe daily dose should not exceed 10,000 iu (250 mcg). Scientists conducting the VITAL (vitamin D and Omega 3) Trial also have chosen a dose of 2,000 iu/day dose for those in the study, who are receiving vitamin D supplements.  However this study is ongoing with results likely in 2021 or beyond.

Irrespective of these recommendations and studies, many physicians recommend higher doses. The safest and most effective way to determine your need for vitamin D and the correct dose, is to consult your medical provider for professional advice.

Movement as the language of emotion: Why Moving Meditations make sense.

By Peter Payne and Mardi Crane-Godreau, Ph.D.

Rational explanations make little difference when a child is wired or anxious. This is especially true for many children on the autism spectrum and can apply equally to many other kids as well. So, is there anything that can help?

Let’s start with some basic neuroscience. The brain communicates on two main levels: the instinctive-emotional-movement level, and the rational-verbal level.  It should be no surprise that we begin life operating on the instinctive-emotional-movement level. The language of the instinctive part of the brain is movement and sensation! As this part of the brain and nervous system develop, the maturation of the rational verbal aspects can more easily follow suit.

There are many supportive therapies and educational programs that strive to help kids who are on the spectrum, develop their nervous systems and the skills that are needed for successful and satisfying everyday living.  The ‘Moving Meditations’ app was designed to provide an easily accessible, low cost, and useful tool for both younger and older kids to support calm and skills for self-regulation. When watching and following along is a shared activity, parents and teachers have reported reduced stress and anxiety for kids and for themselves.  

‘Moving Meditations’ app uses movement to help to discharge stress and to build neurological awareness.   Inspired by ASD pioneers, and backed by neuroscience, the app includes a series of short (1 ½ to 2 minute) videos, which show a child doing various simple self-care movements. These images are accompanied by nature scenes, special effects, and music, to create a fascinating and mesmerizing flow of imagery which draw the watcher in to a calmer, more present state, and restore balance to the  nervous system.

The watcher may be moved to imitate the motions that are shown. Similar to imitating the movements of Tai Chi, this can be very beneficial. These simple movements (with or without the videos) can be used at any time to help to support inner balance. For those striving to find tools to promote self-regulation, we made these videos especially for you.

This project was inspired by the work of pioneer autism researcher, Dr. Louisa Silva, who discovered that meaningful support and communications could be established with the nervous systems of children with autism, even severe autism, by training parents to use specific and regular patterns of touch and body movements. In a series of scientific papers, she documented evidence of the results from tests of her method (called Qigong Sensory Training, or QST for short). Anat Baniel independently discovered much the same thing; by tuning in to the child’s movements and interacting through touch and sound, the child’s nervous system calms down and re-organizes itself, with  improvements in behavior and communication. Neither system denies the importance of understanding the genetic and brain changes involved in ASD and other developmental challenges; but they have found that despite these issues, approaching the child through movement and sensation can help restore a balanced nervous system and bring calm and presence.

Moving Meditations draws on neuroscience and pragmatic research.  Download the app today.

Feel free to contact us with questions or feedback at Bodymindscience4Research@gmail.com

Moving Meditations: a stress reduction tool for families with autism

From BodyMind Science

Mardi Crane-Godreau, PhD

Experts agree that stress and anxiety are common challenges for families with autism. Stress is linked to many health issues that can create roadblocks to leaning and well-being. Aware of this issue, we’ve been working on an app that we hope will help to address some of the challenges.

In 2015 I began working with a family whose 7 year old son had been diagnosed with autism five years earlier.  Despite dedicated and loving attention from both parents, and support from specialists and the best professional advice available, efforts to find solutions to their son’s lack of self-regulation and frequent anxiety and panic were ongoing challenges. My involvement began by teaching the parents the QST method of tactile-movement therapy that they began to administer on a daily basis. Their son’s language, social skills, and digestion improved and his anxiety began to diminish. But as he began to mature, he began to resist the daily parental therapy, except in times of special need, when he would seek it out.

Self-regulation skills and continued neurological developmental support were still needed.  I wondered if watching and mimicking another child doing gentle but meaningful movements might be useful.  A colleague, Peter Payne and I selected movement practices based on research demonstrating benefit to adults with nervous system dysregulation.  (The research from our lab at Dartmouth has shown significant improvement in health and wellbeing of adults who have taken part in long term body-awareness training.)

Our adult oriented training videos would not be meaningful for most kids, so we dug into the problem and began to make short child friendly videos backed by music, special effects and by scenes from nature. Some of the special effects include ‘stims’ designed to attract and hold the attention of children with autism. A few prototype videos were made available to the family, who began to use them, not just on a tablet or phone, but also projected on the TV screen with the whole family taking part.   The child’s special education teacher and his school also began to use the videos to calm him at times of high anxiety.

For this child, who has now had the use and support of videos for more than 18 months, his parents report marked decrease in anxiety and continued improvement in language and social skills. Separation anxiety and panic attacks are now rare events. While the videos are reported to have an immediate calming effect for him and other children who are now using them, his self-regulation and language skills continue to increase gradually. We hope that more families and teachers will give the Moving Meditations app a try.

Moving Meditations for Families with Autism is available for Android and Apple devices. It contains 18 short videos that address 6 separate goals. It is suitable for most kids to watch by themselves, but we encourage family participation with parents or siblings also taking part in a brief but enjoyable activity. Some teachers may also find this suitable for classroom use.

We need your feedback! Download the app to your phone or tablet today.  Try it with your child.   Submit your ratings and comments.  Your experience will help us improve this product and learn more about its benefits and limitations. Your input can help thousands of other families decide how to use this tool.  Thanks for your support! Please shop using the buttons below.

Free installation at the App Store and on Google Play.