New Research From the Alcorn Lab Ties Antibody Deficiency To More Aggressive Immune Response and Greater Lung Injury in Postinfluenza Bacterial Pneumonia
September 10, 2025
A new study from the Alcorn Lab in the Division of Pediatric Pulmonary Medicine at UPMC Children’s Hospital of Pittsburgh, published in The Journal of Clinical Investigation, found that the absence of B cell–derived antibody after influenza infection triggers an overly aggressive CD8+ T-cell response contributing to more lung inflammation and injury during a secondary bacterial pneumonia. John Alcorn, PhD, ATSF, professor of Pediatrics and Immunology, vice chair of Basic Research, and associate director of the RK Mellon Institute for Pediatric Research, was senior author of the study.
Looking at Immune Memory Through a Different Lens
Secondary bacterial pneumonia is a serious complication of influenza, particularly in young children and other vulnerable patient populations. Most people have some level of prior immunity to influenza but what that means for subsequent bacterial infection risk is not always straightforward. The study from Dr. Alcorn and colleagues was designed to investigate how different components of immune memory, especially B cell antibody production, can influence the lung’s response to a second infection.
“This work was about identifying how the different arms of the immune system compensate for each other in the lung after influenza,” says Dr. Alcorn. “We wanted to understand what happens when antibody is missing and how that affects the broader immune response to a second infection.”
A Protective Response, but With a Cost
Without antibody, CD8+ T-cells became more cytotoxic in the lung. These T-cells helped control bacterial infection early but also caused more inflammation, increased protein leak into the airways, and more damage to the surrounding tissue. Models with intact antibody responses sustained a more balanced response and experienced significantly less injury.
Dr. Alcorn’s team, led Leigh Miller, PhD, MSPH, also showed that transferring influenza-immune serum into antibody-deficient models restored the balance. The intervention reduced the CD8+ T cell response and limited inflammation. These results also held up in superinfection models using both Staphylococcus aureus and Klebsiella pneumoniae, pointing to a more generalizable immune mechanism.
“When antibody is absent, the immune system relies more heavily on CD8+ T cells,” Dr. Alcorn says. “That gets the job done in terms of controlling viral infection, but it also results in more tissue injury. Antibody seems to regulate that response in a protective way. Maintaining the balance of protection from infection with not injury the delicate lung tissue is essential.”
Implications for Patients With Impaired Humoral Immunity
The findings from Dr. Alcorn’s lab may help explain why some patients with B cell deficiencies, or those receiving B cell–depleting therapies for things like cancer, are at increased risk for pulmonary complications after a bout of influenza. The immune system compensates in ways that preserve host defense, but sometimes at the expense of tissue integrity.
“This gives us another way to think about patients with compromised humoral immunity,” Dr. Alcorn says. “In these cases, it may not just be that they have less protection but rather that their immune system is compensating in a way that causes more damage.”
The results of the research also reinforce the importance of vaccination against influenza, which has proven efficacy and safety over decades of use and research, and it also suggests that passive antibody strategies may have value in certain populations at risk for severe complications.
Read or download a full copy of the open access paper using the link below.
Study Reference
