The presence of a certain molecule allows the immune system to effectively police tuberculosis (TB) of the lungs and prevent it from turning into an active and deadly infection, according to a new study led by researchers at Children's Hospital of Pittsburgh of UPMC and the University of Pittsburgh School of Medicine. Their findings appear today in the online version of the Journal of Clinical Investigation.
More than 2 billion people or one-third of the world's population are infected with mycobacterium tuberculosis, the bacterium that causes TB, says senior author Shabaana A. Khader, PhD, assistant professor of pediatrics, Pitt School of Medicine. The infection is challenging to treat partly because the bacillus is able to enter cells and linger for years without causing symptoms, known as latent TB. Then, typically when the immune system becomes impaired due to other reasons such as age or HIV, the infection becomes active and causes the cough, night sweats, fever and weight loss that characterize the disease.
"A hallmark of TB that we see on chest X-rays is the granuloma, a collection of immune cells that surround the infected lung cells," Khader says. "But what we didn't know was the difference between a functioning protective granulomae, as in latent TB, and a non-protective granuloma seen in active TB patients. We aimed to find immunologic markers that could show us the status of the infection."
For the study, which was funded by the National Institutes of Health, the researchers studied human TB-infected cells as well animal models of the disease. They found that granulomas that contain ectopic lymphoid structures, which resemble lymph nodes, are associated with effective suppression of TB, and that granulomas that don't contain them are associated with active TB. They also learned that immune cells called T cells that had a surface marker molecule called CXCR5 were associated with the presence of ectopic lymphoid structures.
It's akin to reporting a break-in, Khader says. If a person calls 911 because of a robbery, but doesn't give a specific address, the immune system police could come to the neighborhood but don't know for certain which home was invaded.
"The presence of CXCR5 provides a specific address for the infected cells that tells the immune cells where to focus their attention to contain the problem," she explains. "That results in the formation of ectopic lymphoid structures and the protective granuloma that keeps TB infection under control, unlike in active disease. Without CXCR5, those structures did not form and active TB was more likely."
When the researchers delivered CXCR5 T cells from donor animals to TB-infected mice that lacked CXCR5, T cell localization and ectopic lymphoid structure formation was restored, leading to decreased susceptibility to TB.
"The protective power of CXCR5 points us in a novel direction for future management of TB," Khader says. "These findings have powerful implications for the development of vaccines to prevent infection."
Co-authors include other researchers from the University of Pittsburgh School of Medicine and Children's Hospital of Pittsburgh of UPMC; the University of Rochester Medical Center; Tulane National Primate Research Center; Instituto Nacional de Enfermedades Respiratorias "Ismael Cosio Villegas," Mexico; "National Institute of Psychiatry "Ramon de la Fuente," Mexico; and The American British Cowdray Medical Center, Mexico.
The study was funded NIH grants AI083541, HL105427, RR026006, AI091457, RR020159, RR000164, HL69409, AI060422, and AI91036 as well as Children's Hospital of Pittsburgh of UPMC.
Dear Helpdesk: Working in a Toxic Health Care Environment
March 28th 2024Dear Helpdesk is your steadfast companion, offering life coaching and workplace advice from 2 seasoned IPs for some of your most challenging real-life situations. Let us help you navigate the intersection between work and life, guiding you to navigate the dynamic world of infection prevention with confidence and grace. This article is on handling a toxic health care environment.
Product Locator: Spring and Early Mother's Day Gift Guide for Infection Prevention Personnel
March 27th 2024Whether it's a spring holiday, birthdays, or no reason at all, infection prevention personnel love to give and receive gifts that help at the end of a stressful day. Infection Control Today® offers some gift ideas for infection prevention personnel and their families.
Catching Up With Vangie Dennis, AORN 2022-2023 President at AORN 2024
March 26th 2024Infection Control Today (ICT) had the privilege of catching up with Vangie Dennis, MSN, RN, CNOR, CMLSO, at the Association of periOperative Registered Nurses' (AORN’s) International Surgical Conference & Expo 2024. As the former president of AORN and an esteemed figure in perioperative services, Vangie Dennis shared insights into her recent endeavors and the exciting new chapter she's embarked upon.
How To Optimize Your Time Management Strategies for the Busy Infection Preventionist
March 25th 2024Is your calendar resembling a chaotic masterpiece of overlapping tasks? Join the club of infection preventionists striving to balance responsibilities. Dive into proven strategies from a fellow infection preventionist to reclaim control of your time, streamline tasks, and boost productivity effectively. This is an IP Lifeline article.