Past exposure to viruses and age could shape a child’s response to acute respiratory tract infections (also known as ARTIs), according to new research led by Children’s Hospital of Philadelphia and the University of Pennsylvania. In a small sample of children who visited the CHOP Emergency Department (ED) with flu-like symptoms, the researchers discovered that the set of genes expressed by anti-viral immune cells (known as CD8 T cells) differed between younger children who had been previously exposed to the flu virus, and those who had not. The severity of the ARTI, asthma, and sex also influenced a child’s response to the infection. Based on their findings, the researchers also developed an Influenza Pediatric Signature (IPS) that distinguishes acute influenza from acute respiratory tract infections caused by other pathogens based on increased or decreased expression of a small set of genes in CD8 T cells of patients with an acute influenza infection.
Why it matters:
ARTIs are the leading cause of death in early childhood worldwide. By better understanding how earlier infections might influence a child’s long-term immune response, particularly with the help of tools like the IPS, researchers and clinicians can advance how they treat and diagnose young patients with the condition. More specifically, linking the basic science of how immune cells express genes to real-life cases in a children’s emergency department can help researchers to discover the key pathways involved in host-pathogen interactions and develop effective treatments for children with severe flu symptoms.
Who conducted the study:
Sarah Henrickson, MD, PhD, an attending physician and instructor in the Division of Allergy and Immunology at CHOP, led the study alongside fellow investigators from the Divisions of Emergency Medicine and Infectious Diseases at CHOP and the Institute for Immunology at the University of Pennsylvania.
How they did it:
The study began during the 2009 H1N1 flu epidemic to discover how host responses change with different viral infections, according to Dr. Henrickson. The team used blood samples from 29 children who visited the CHOP ED with flu symptoms. Based on the information gathered, the investigators were able to develop the IPS using healthy controls and published influenza transcriptional datasets.
“The notion that an individual’s capacity to combat the flu depends on what they have been exposed to in the past, especially early in life, has been gaining momentum,” said E. John Wherry, PhD, director of the Institute for Immunology at Penn and the study’s senior author in a press release. “Although this IPS is unlikely to replace clinical virological diagnosis anytime soon, the strength of the IPS score may reflect the severity of disease and provide helpful information post infection.”
Dr. Henrickson will continue focus on T cell dysfunction in pediatric disease, including investigating the impact of chronic inflammation (with obesity and asthma) and recurrent infection (with primary immunodeficiency) on immune function.
Where the study was published:
The researchers published the study in Cell Reports.
Where to learn more:
Read the full press statement from Penn Medicine, and learn about Dr. Henrickson’s previous research into uncovering the immune system’s secrets on Cornerstone.