by Researchers from the University of Pittsburgh Center for Vaccine Research have made a significant discovery regarding the role of immune cells in tuberculosis (TB) infection. The study, published in the Journal of Experimental Medicine, reveals that innate CD8+ lymphocytes, a subtype of white blood cells involved in rapid immune response, are essential in controlling the disease. Additionally, the researchers identified an inflammatory molecule called Interleukin-15 (IL-15) that plays a crucial role in infection control and could potentially enhance the efficacy of existing and future TB vaccines.
Senior author JoAnne Flynn, Ph.D., distinguished professor and chair of microbiology and molecular genetics at Pitt, described the finding as unusual, stating that no one before them had shown that CD8+ lymphocytes have a significant impact early on in the infection. However, the researchers’ findings suggest that these innate immune cell populations play an important role in restraining the initial infection.
TB is an airborne lung disease caused by the bacterium Mycobacterium tuberculosis. Following the entry of these bacteria into the lung, the infection spreads, prompting the body to initiate an immune response and form clusters of immune cells, known as granulomas, to control the infection and minimize damage to the lungs.
The immune response in tuberculosis infection consists of two phases. The first six weeks involve the influx of fast-acting immune cells to the site of infection, aiming to quickly kill the bacteria and limit damage. The second phase, which occurs after eight to 10 weeks, involves the adaptive immune response, which precisely targets the infection-causing pathogen and focuses on efficient elimination. However, the exact dynamics of the immune response and the role of CD8+ lymphocytes in the early stages of tuberculosis were previously unclear.
The researchers found that infection progressed more rapidly and spread further in macaque monkeys with depleted innate CD8+ cells compared to monkeys with intact CD8+ T cell population or those with removed adaptive CD8+ T cells. This suggests that innate CD8+ cells play a critical role in limiting the infection in its early stages.
Using a technique called bacterium barcoding, researchers traced the lineages of bacterial granulomas formed during the disease. In animals lacking innate CD8+ cells, they identified more bacterial dissemination across the lungs and lymph nodes, indicating that these cells act as a “bottleneck,” preventing bacteria from establishing an active infection.
Interestingly, the study also revealed that in monkeys with depleted innate CD8+ cells, other immune cells attempted to compensate for the lack of fast responders, possibly in response to IL-15. However, these cells lack the natural mechanisms necessary to deliver molecules that can kill the bacterium, resulting in an incomplete infection-clearing immune response.
In their next phase of research, scientists will investigate whether administering IL-15 alongside an existing TB vaccine can enhance protection and increase the vaccine’s effectiveness.
Note:
- Source: Coherent Market Insights, Public sources, Desk research
- We have leveraged AI tools to mine information and compile it
