Team shows how childhood viral infection leads to increased risk for allergic asthma as adult

September 12, 2012

(Medical Xpress)—Researchers in the Division of Pulmonary, Allergy and Critical Care Medicine at the University of Pittsburgh School of Medicine have shown in an animal model that a common childhood virus disables the normal immune tolerance transferred from the mother to child through breast milk, leading to increased susceptibility for allergic asthma later in life. Their findings were reported in the online version of Nature Medicine.

Early in life, , or Treg, play an important role in the establishment of , which can prevent the immune system from triggering an allergic reaction to antigens such as pollen and dust, explained senior authors Anuradha Ray, Ph.D., and Prabir Ray, Ph.D., both professors of medicine and immunology, Pitt School of Medicine.

"We know that recurrent infections by (RSV) that require hospitalization in early life increase the risk for asthma in ," noted Dr. Anuradha Ray. "But, until now, it hasn't been clear why this happens."

Allergens and biologic molecules that suppress the immune system are transferred from mothers to infants via breast milk, which induces protective regulatory Tregs in the infants to help block the development of later in life, such as asthma.

"So we went from 'bedside to bench' to better understand the immunological impact of early, repeated RSV infection and to see if it affects Tregs," explained lead author, Nandini Krishnamoorthy, Ph.D., postdoctoral associate, Division of Pulmonary, Allergy and Critical Care Medicine, Pitt School of Medicine.

First, the research team fed newborn mice with from their mothers, who in turn had been exposed to the egg-white protein ovalbumin every other day for 10 days, to see if the babies would become tolerant to the protein. The newborn mice were weaned after 21 days, and then some of them were infected with RSV several times for the next three weeks to mimic human infection. In the sixth week, the young mice were challenged with ovalbumin.

Mice that had not been infected with RSV did not have an immune response to the ovalbumin, to which they had been exposed through their mothers' milk, indicating they had developed tolerance for it. Those that had been repeatedly infected with RSV, however, had increased immune cell infiltration in their airways and increased mucus production when challenged with the egg protein.

In another experiment, Treg cells were isolated from either the RSV-infected or uninfected mice and transferred into ovalbumin-exposed animals, which were then challenged with the protein. The cells from the uninfected mice, but not those from the infected ones, potently prevented airway inflammation and other markers of allergic reaction, the researchers found. They also noted that RSV promoted the production of regulatory proteins called cytokines that foster inflammation, as well as triggered other changes in the cellular microenvironment altering the function of Treg cells.

"So without the suppressive function of the Tregs, the mice developed inflammatory immune responses to the ovalbumin allergen and developed asthma-like symptoms," said Dr. Prabir Ray, who initiated the study. "If the memory Tregs are crippled early in life, an important protective mechanism against allergens is lost, which increases susceptibility to asthma."

"These studies suggest a link between early RSV viral infection and the development of adult allergy via direct effects of the virus infection on the very important regulatory T cell," said Mark T. Gladwin, M.D., chief of the Division of Pulmonary, Allergy and , Pitt School of Medicine and UPMC.  "From a clinical standpoint, efforts to control RSV infection or to enhance activation of regulatory T cells with breastfeeding and other strategies appear to be a promising approach to reducing our current asthma and allergy epidemic."

Explore further: Dog-associated house dust protects against respiratory infection linked to asthma

Related Stories

Dog-associated house dust protects against respiratory infection linked to asthma

June 19, 2012
House dust from homes with dogs appears to protect against infection with a common respiratory virus that is associated with the development of asthma in children. Researchers from the University of California, San Francisco, ...

Researchers map pathway of infection for a common, potentially life-threatening respiratory virus

August 15, 2011
Researchers at the University of Toronto, The Hospital for Sick Children (SickKids), St. Paul's Hospital and the University of British Columbia have identified a new treatment target for a virus that causes severe lung infections ...

Gastric bacterium Helicobacter pylori protects against asthma

July 1, 2011
Infection with the gastric bacterium Helicobacter pylori provides reliable protection against allergy-induced asthma, immunologists from the University of Zurich have demonstrated in an animal model together with allergy ...

Recommended for you

Genetic immune deficiency could hold key to severe childhood infections

July 18, 2017
A gene mutation making young children extremely vulnerable to common viruses may represent a new type of immunodeficiency, according to a University of Queensland researcher.

What are the best ways to diagnose and manage asthma?

July 18, 2017
What are the best ways to diagnose and manage asthma in adults? This can be tricky because asthma can stem from several causes and treatment often depends on what is triggering the asthma.

Large multi-ethnic study identifies many new genetic markers for lupus

July 17, 2017
Scientists from an international consortium have identified a large number of new genetic markers that predispose individuals to lupus.

Study finds molecular explanation for struggles of obese asthmatics

July 17, 2017
A large, bouquet-shaped molecule called surfactant protein A, or SP-A, may explain why obese asthma patients have harder-to-treat symptoms than their lean and overweight counterparts, according to a new study led by scientists ...

Team identifies potential cause for lupus

July 14, 2017
Leading rheumatologist and Feinstein Institute for Medical Research Professor Betty Diamond, MD, may have identified a protein as a cause for the adverse reaction of the immune system in patients suffering from lupus. A better ...

Immunosuppression underlies resistance to anti-angiogenic therapy

July 14, 2017
A Massachusetts General Hospital (MGH) research team has identified a novel mechanism behind resistance to angiogenesis inhibitors - drugs that fight cancer by suppressing the formation of new blood vessels. In their report ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

shaon
not rated yet Sep 15, 2012
thanks for sharing a helpful information. i also have allergic problem not by born.my question is if anybody have this problem by born,whats the solve permanently.

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.