The role of interleukin (IL)-10 in the persistence of Leishmania major in the skin after healing and the therapeutic potential of anti-IL-10 receptorantibody for sterile cure

Some pathogens (e.g., Mycobacterium tuberculosis, Toxoplasma gondii, Leishm ania spp) have been shown to persist in their host after clinical cure, est ablishing the risk of disease reactivation. We analyzed the conditions nece ssary for the long term maintenance of Leishmania major in genetically resi stant C57BL/6 mice after spontaneous healing of their dermal lesions. Inter leukin (IL)-10 was found to play an essential role in parasite persistence as sterile cure was achieved in IL-10-deficient and IL-4/IL-10 double-defic ient mice. The requirement for IL-10 in establishing latency associated wit h natural infection was confirmed in IL-10-deficient mice challenged by bit e of infected sand flies. The host-parasite equilibrium was maintained by C D4(+) and CD8(+) T cells which were each able to release IL-10 or interfero n (IFN)-gamma, and were found to accumulate in chronic sites of infection, including the skin and draining lymph node. A high frequency of the dermal CD4(+) T cells released both IL-10 and IFN-gamma. Wild-type mice treated tr ansiently during the chronic phase with anti-IL-10 receptor antibodies achi eved sterile cure, suggesting a novel therapeutic approach to eliminate lat ency, infection reservoirs, and the risk of reactivation disease.