Identifying underlying causes of immune deficiencies that increase shingles risk

June 12, 2017, JCI Journals

Early life infections with varicella zoster virus cause chickenpox, but the virus can remain dormant in the nervous system for decades and reactivate to cause herpes zoster, commonly known as shingles. Shingles is characterized by a painful skin rash and blisters, and it predominantly affects the elderly. Shingles also occurs at a higher rate in people diagnosed with coronary artery disease (CAD), which affects immune system function in part through changes in infection-responsive immune cells called macrophages. The specific immune mechanisms underlying age- and CAD-related viral reactivation are not well understood.

This week in the JCI, a study led by Cornelia Weyand at Stanford University reports that macrophages derived from individuals diagnosed with CAD suppress the activation and proliferation of T cells. Excessive accumulation of the metabolic intermediate pyruvate in these macrophages increased expression of a signaling molecule called PD-L1 that drives T cell suppression. The overabundance of pyruvate in macrophages suggests that metabolic dysregulation may contribute to immune dysfunction in individuals affected by CAD.

The activity of this immunosuppressive pathway in CAD patients provides insights into a mechanism for immune deficiencies that permit reactivation of long-latent viruses. These findings are a step toward developing new strategies that correct metabolic dysregulation in immune cells to prevent shingles and other infections in at-risk populations.

Explore further: Shingles increases short-term risk of stroke in older adults

More information: Ryu Watanabe et al, Pyruvate controls the checkpoint inhibitor PD-L1 and suppresses T cell immunity, Journal of Clinical Investigation (2017). DOI: 10.1172/JCI92167

Related Stories

Shingles increases short-term risk of stroke in older adults

December 15, 2015
More than 95% of the world's adult population is infected with the virus that causes chickenpox. Up to one third of these individuals will develop shingles (herpes zoster) in their lifetime. A new U.S. study has found that ...

Childhood asthma may increase risks of shingles

December 28, 2015
Nearly 1 million incidences of herpes zoster, which is also known as shingles, occur every year in the U.S., with an estimated one-third of all adults affected by age 80. Despite its prevalence, particularly between ages ...

Viral protein may help chickenpox virus spread within the body

May 25, 2017
The virus that causes chickenpox—varicella zoster virus (VZV)—possesses a protein that could enhance its ability to hijack white blood cells and spread throughout the body, according to new research published in PLOS ...

New study finds shingles vaccine remains effective after chemotherapy

August 5, 2014
The herpes zoster vaccine continues to be effective in protecting older adults against shingles, even after they undergo chemotherapy, according to a Kaiser Permanente study published today in the journal Clinical Infectious ...

Chickenpox vaccine not responsible for rise in shingles, study says

December 2, 2013
(HealthDay)—The prevalence of a painful condition known as shingles is increasing in the United States, but new research says the chickenpox vaccine isn't to blame.

Recommended for you

Research debunks 'myth' that strenuous exercise suppresses the immune system

April 20, 2018
New research overturns a myth that has persisted for nearly four decades - that competing in endurance sports, like this weekend's London Marathon, suppresses the body's immune system and makes competitors more susceptible ...

Immune diversity among the KhoeSan population

April 20, 2018
A new study of the KhoeSan of Southern Africa has improved the understanding of immune diversity among the oldest surviving indigenous population in the world.

Psoriasis treated with compound derived from immune cells

April 18, 2018
A compound derived from immune cells treats psoriasis in mice and holds promise for other autoimmune diseases, according to a new study from Washington University School of Medicine in St. Louis.

Researchers uncover origin of virus-fighting plasma B cells

April 18, 2018
Plasma B cells, which move through the body releasing antibodies, are an important component of the body's fight against viral infections and other invaders. They are relatively rare, however, and increasing their ranks is ...

New disease model to facilitate development of ALS and MS therapies

April 17, 2018
Researchers at Karolinska Institutet in Sweden have developed a new disease model for neurodegenerative diseases such as ALS and MS that can be used to develop new immunotherapies. The model is described in a publication ...

Your immune system holds the line against repeat invaders, thanks to this molecule

April 17, 2018
Memory T cells are a critical element of our immune system's historical archive. To prevent repeat infections, these cells retain a record of germs they've fought before.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.