CCR4LEP: Exploring CCR4 as immune correlate of protection for leprosy
Led by Dr Anouk van Hooij (Leiden University Medical Center, the Netherlands), with Dr Abu Sufian Chowdhury (International, Bangladesh)
Project Aim
Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which can lead to nerve damage and lifelong disabilities. Today, more than 4 million people suffer from permanent leprosy-associated disabilities and handicaps. There is no specific vaccine available for leprosy, though the tuberculosis vaccine BCG provides partial protection against leprosy. Clinical presentation of leprosy varies from patients presenting with few bacteria (paucibacillary/PB) to widespread infection (multibacillary/MB). Although it is known that these disease presentations are determined by the immune response of patients to the bacteria, the exact immune factors protecting individuals from developing leprosy remain to be elucidated. Our recent research suggests that a protein called CCR4, found on immune cells, plays a role in controlling the growth of M. leprae. Compared to MB patients, CCR4 was more frequently observed on immune cells of PB patients and contacts who had been exposed to the bacterium, but did not develop disease. Additionally, immune cells of contacts induced more CCL22, a molecule that interacts with CCR4, compared to patients.
This project aims to explore the CCR4-CCL22 interaction further, by studying its role in the protective immune response against leprosy. The effect of exposure to M. leprae on this immune response, as well as the effect of removing the bacterial burden by effective treatment of patients will be determined. For this purpose, immune cells of leprosy patients, their contacts, and unexposed individuals will be extensively analysed by advanced immunological methods. The project will also examine how blocking CCR4 affects the ability of immune cells to inhibit the growth of mycobacteria in the lab. Ultimately, the proposed project aims to identify immune factors that protect exposed individuals from leprosy, which could guide the development of vaccine candidates or other preventive treatments.
