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 receptor antibody for sterile cure

Yasmine Belkaid, Karl F. Hoffmann, Susana Mendez, Shaden Kamhawi, Mark C. Udey, Tom A. Wynn, David L. Sacks

Research output: Contribution to journalArticlepeer-review

469 Scopus citations

Abstract

Some pathogens (e.g., Mycobacterium tuberculosis, Toxoplasma gondii, Leishmania spp) have been shown to persist in their host after clinical cure, establishing the risk of disease reactivation. We analyzed the conditions necessary for the long term maintenance of Leishmania major in genetically resistant C57BL/6 mice after spontaneous healing of their dermal lesions. Interleukin (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-deficient mice. The requirement for IL-10 in establishing latency associated with natural infection was confirmed in IL-10-deficient mice challenged by bite of infected sand flies. The host-parasite equilibrium was maintained by CD4+ and CD8+ T cells which were each able to release IL-10 or interferon (IFN)-γ, 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-γ. Wild-type mice treated transiently during the chronic phase with anti-IL-10 receptor antibodies achieved sterile cure, suggesting a novel therapeutic approach to eliminate latency, infection reservoirs, and the risk of reactivation disease.

Original languageEnglish
Pages (from-to)1497-1506
Number of pages10
JournalJournal of Experimental Medicine
Volume194
Issue number10
DOIs
StatePublished - Nov 19 2001

Keywords

  • CD8T cells
  • Chronic infection
  • IL-10
  • Leishmania major
  • Skin

Fingerprint

Dive into the research topics of '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 receptor antibody for sterile cure'. Together they form a unique fingerprint.

Cite this