Immune system prioritizes distinct immune responses in infants with flu

August 28, 2018, St. Jude Children's Research Hospital
A 3-D image of a flu virus. Credit: Center for Disease Control

The immune system appears to put a premium on maintaining lung function in infants infected with the influenza virus by mounting a rapid response to repair damaged cells, according to research led by St. Jude Children's Research Hospital. The findings appear today in the scientific journal Immunity.

Researchers reported evidence that unconventional T cells play a pivotal role in protecting from serious, possibly fatal, flu complications. Rather than fueling inflammation, the unconventional T cells triggered a biochemical cascade that increased levels of a growth hormone essential for repair of damaged by the infection.

"The stakes are higher for infants with flu infections than for older children and adults," said corresponding author Paul Thomas, Ph.D., a member of the St. Jude Department of Immunology. "Flu is an acute respiratory infection. Compared to adults, infant lungs are smaller and young children are more likely to develop severe, sometimes deadly complications, that require hospitalization and lead to higher mortality rates.

"This study suggests the immune response to flu infections varies between infants and older patients and uses a distinct route for repair and restoration of ," he said. "The work also identifies a pathway to target in the future using therapies to ease in infants."

Infant T cells

T cells help the immune system mount and regulate the response to viruses and other threats. The cells are classified partly based on protein chains that make up the cell surface receptors. One type of unconventional T cell receptor has gamma (γ) and delta (δ) protein chains. Conventional T cell receptors have different proteins.

While conventional T cells are developmentally immature at birth, γδ T cells develop before birth and are ready to respond rapidly to a wide range of infectious agents. The γδ T cells are concentrated in the cells lining the lungs, gut, skin and other barrier tissues.

The role of γδ T cells in combating flu, particularly in infants and young children, was unclear. In fact, based on previous research, γ? T cells were more associated with driving inflammation than with promoting cell repair.

Promoting repair

But results of this research told a different story. Thomas and his colleagues reported the γδ T cells that accumulated in response to flu infection in week-old mice produced increased amounts of a signaling protein (cytokine) called interleukin-17A. Investigators showed how increased IL-17A fueled increased production of another signaling protein, the cytokine interleukin-33 in the lining the lungs. IL-33 recruits other , including regulatory T cells and innate lymphoid cell. These immune cells produce the growth factor amphiregulin, which promotes cell repair.

Loss of γδ T cells did not affect the ability of newborn mice to eliminate the flu virus or to produce interferon-γ, a cytokine that promotes inflammation. However, death rates were higher in the mice lacking γ? T cells that produced IL-17A or the gene for IL-33.

Researchers also found evidence of the same system at work in young flu patients. An analysis of nasal fluid from 25 infants with confirmed flu infections revealed that IL-17A, IL-33 and amphiregulin levels were correlated. Increased IL-17A was also associated with better patient outcomes.

"Previous research has suggested that γ? T cells did not play a significant role in , particularly in adults," said first author Xi-zhi Guo, a graduate student in Thomas' laboratory. "But we thought that might be because γδ T cells are special. They develop in utero and maybe their role is to help protect right after birth while conventional T are still developing."

Thomas added: "These results suggest the body utilizes a distinct mechanism for tissue repair and restoration of lung function in infants compared to adults."

Explore further: Scientists identify a protein complex that shapes the destiny of T cells

Related Stories

Scientists identify a protein complex that shapes the destiny of T cells

July 6, 2018
Like a mentor helping medical students choose between specialties, a protein complex helps shape the destiny of developing T cells, St. Jude Children's Research Hospital scientists have reported. The research appears today ...

Revving up innate control of viral infection requires a three-cell ignition

July 5, 2018
One of the most important cell types for controlling certain viral infections are natural killer (NK) cells. As part of the innate and rapid immune response, NK-cell recruitment and activation was thought to be a straightforward ...

Rebooting the system: Immune cells repair damaged lung tissues after flu infection

October 3, 2011
There's more than one way to mop up after a flu infection. Now, researchers from the Perelman School of Medicine at the University of Pennsylvania report in Nature Immunology that a previously unrecognized population of lung ...

Research identifies unconventional immune cell capable of fighting viral infections

May 2, 2018
Research led by the University of Birmingham has identified a novel unconventional type of immune cell capable of fighting viral infections.

Infants born preterm may lack key lung cells later in life

June 9, 2017
Mice born into an oxygen-rich environment respond worse to the flu once fully grown due to an absence of certain lung cells, a discovery that provides a potential explanation for preterm infants' added susceptibility to influenza ...

Allergies? Exhausted regulatory T cells may play a role

August 24, 2017
Researchers have evidence that the specialized T cells responsible for maintaining a balanced immune response are vulnerable to exhaustion that disrupts normal functioning and may even contribute to allergic reactions. St. ...

Recommended for you

Immunity connects gut bacteria and aging

November 13, 2018
Over the years, researchers have learned that the different populations of bacteria that inhabit the gut have significant effects on body functions, including the immune system. The populations of gut bacteria are sometimes ...

Probiotics increase bone volume in healthy mice

November 13, 2018
A widely-used probiotic stimulates bone formation in young female mice, according to a study published November 13th in the journal Immunity. In response to treatment with Lactobacillus rhamnosus GG (LGG), other intestinal ...

An enzyme in immune cells plays essential role in host defense against tuberculosis

November 13, 2018
Using freshly resected lung tissue from 21 patients and two distinct mouse models, tuberculosis researchers at the University of Alabama at Birmingham and the Africa Health Research Institute, or AHRI, have identified a protein ...

Study shows changes in histone methylation patterns in nutritionally stunted children

November 13, 2018
An international team of researchers has found changes in histone methylation patterns in nutritionally stunted children. In their paper published in Proceedings of the National Academy of Sciences, the group describes their ...

New clues to the origin and progression of multiple sclerosis

November 13, 2018
Mapping of a certain group of cells, known as oligodendrocytes, in the central nervous system of a mouse model of multiple sclerosis (MS), shows that they might have a significant role in the development of the disease. The ...

Cognitive decline—radiation—brain tumor prevented by temporarily shutting down immune response

November 13, 2018
Treating brain tumors comes at a steep cost, especially for children. More than half of patients who endure radiation therapy for these tumors experience irreversible cognitive decline, a side-effect that has particularly ...

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.