What makes the newborn immune system in the lungs different and vulnerable?

February 13, 2014

Newborns are more susceptible to infections, presumably because of their immature and inexperienced immune systems. The most common dangerous condition in newborns and infants are lower respiratory tract infections caused by viruses, especially respiratory syncytial virus (RSV). A study published on February 13th in PLOS Pathogens shows how the immune system in the lungs during early life differs from the one in older children and adults.

Ideally, newborns could be protected against RSV by vaccination, but it is known that the in early life is less responsive to "conventional" vaccines. Barney Graham and colleagues, from the US National Institute of Allergy and Infectious Diseases, are working on understanding the early immune system in order to develop effective vaccines for newborns and infants.

The to virus infection in the lung involves mobile called dendritic (or DCs). After contact with a viral intruder, the DCs move into adjacent where they activate another type of immune cell, called CD8+ T cells, and thereby orchestrate a massive, body-wide, virus-specific attack. Graham and colleagues studied the behavior of these lung DCs in newborn mice and compared it with that in older animals.

They found that the lung DC responses following RSV infection undergo dramatic changes during the first weeks of life. One of the two subsets active in adults was present in low numbers and functionally limited in newborn mice. The second subset, called CD103+ DCs, is present in similar numbers in newborn and adults after virus infection. Following migration to the lymph nodes, CD103+ DCs initiate CD8+ T cell responses. However, when newborn CD103+ DCs and CD8+ T cells interact, the results are very different from the same interaction in older mice.

Depending on the age of the mice at the time of RSV infection, the CD103 DCs activate different subsets of CD8+ T cells. This suggests that DCs from newborns take up, digest, and present parts of an intruding virus to other immune cells in a fundamentally different way than in adults. In addition, the researchers found that CD103+ DCs from newborn mice have much lower expression of two critical "co-stimulatory" molecules (called CD80 and CD86) on their surface. These co-stimulators directly interact with a counterpart (called CD28) on the CD8+ T cells and in doing so boost the immune response, something that is severely impaired in neonatal mice. Dampening CD28-mediated stimulation in adult mice demonstrated that limited CD28-mediated co-stimulatory support from neonatal DCs may constitute one mechanism by which newborn and adult DCs induce distinct CD8+ T cell responses.

"A better understanding of deficiencies in early-life immunity will guide vaccine approaches that induce disease-sparing immune responses in infants", the researchers say. "Our data suggest that the CD80/CD86-CD28 axis may be exploited in the design of pediatric vaccines to promote the generation of more "adult-like" immune responses".

Explore further: Immunology: White blood cells show their stripes

More information: Ruckwardt TJ, Malloy AMW, Morabito KM, Graham BS (2014) Quantitative and Qualitative Deficits in Neonatal Lung-Migratory Dendritic Cells Impact the Generation of the CD8+ T Cell Response. PLoS Pathog 10(2): e1003934. DOI: 10.1371/journal.ppat.1003934

Related Stories

Immunology: White blood cells show their stripes

August 28, 2013
For the human immune system to work effectively, the body must be able to distinguish invading pathogens, such as fungi and bacteria, from its own healthy tissue. A group of white blood cells known as dendritic cells (DCs) ...

Jump-starting cheaper cancer vaccines

September 26, 2012
Dendritic cells (DCs)—workhorses of the immune system—derived from human embryonic stem cells (hESCs) may provide an economical way of generating off-the-shelf therapeutic vaccines against cancers, according to research ...

Discovery of a new class of white blood cells uncovers target for better vaccine design

July 17, 2013
(Medical Xpress)—Scientists at A*STAR's Singapore Immunology Network (SIgN) have discovered a new class of white blood cells in human lung and gut tissues that play a critical role as the first line of defence against harmful ...

Rare immune cell is asset and liability in fighting infection

August 26, 2011
The same trait that makes a rare immune cell invaluable in fighting some infections also can be exploited by other diseases to cause harm, two new studies show.

Study uncovers new explanation for infection susceptibility in newborns

November 6, 2013
Cells that allow helpful bacteria to safely colonize the intestines of newborn infants also suppress their immune systems to make them more vulnerable to infections, according to new research in Nature.

Recommended for you

New vaccine production could improve flu shot accuracy

July 24, 2017
A new way of producing the seasonal flu vaccine could speed up the process and provide better protection against infection.

Molecular hitchhiker on human protein signals tumors to self-destruct

July 24, 2017
Powerful molecules can hitch rides on a plentiful human protein and signal tumors to self-destruct, a team of Vanderbilt University engineers found.

Researchers develop new method to generate human antibodies

July 24, 2017
An international team of scientists has developed a method to rapidly produce specific human antibodies in the laboratory. The technique, which will be described in a paper to be published July 24 in The Journal of Experimental ...

A sodium surprise: Engineers find unexpected result during cardiac research

July 20, 2017
Irregular heartbeat—or arrhythmia—can have sudden and often fatal consequences. A biomedical engineering team at Washington University in St. Louis examining molecular behavior in cardiac tissue recently made a surprising ...

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

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.