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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

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Belkaid, Yasmine, Hoffmann, Karl F., Mendez, Susana, Kamhawi, Shaden, Udey, Mark C., Wynn, Tom A., Sacks, David L.·2001·The Journal of Experimental Medicine
DOI 10.1084/jem.194.10.1497PMC PMC2193677
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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.

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  • Infection of recruited inflammatory monocytes and resident macrophages can induce IL-10 secretion, which fosters the immunosuppressive environment observed in chronic infection.

    “Infection of recruited inflammatory monocytes and resident macrophages can induce IL-10 secretion, which fosters the immunosuppressive environment observed in chronic infection (124, 125).”

    From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [124]

    The Discussion (page unavailable) says Leishmania can prime host macrophages to produce IL-10 in response to a second activation signal, and describes IL-10 as suppressive and important to parasite persistence. It does not identify recruited inflammatory monocytes or resident macrophages as the IL-10-producing populations; it also says CD4+ T cells appear to be the main IL-10 producers in the dermis. (LLM, conf=0.86)

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Authors
Belkaid, Y., Hoffmann, K. F., Mendez, S., Kamhawi, S., Udey, M. C., Wynn, T. A., & Sacks, D. L.
Affiliations
  • National Institute of Allergy and Infectious Diseases (US)
  • 1Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases
  • National Institutes of Health (US)
ORCID
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2001-11-19
Volume
194
Issue
10
Pages
1497-1506
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.194.10.1497
PMC
PMC2193677
OpenAlex
W2116394003
Cited by
557
References
1
Citations by year
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FWCI
33.09
Type
journal article
Language
en
Open access
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
  • Health Sciences › Medicine › Infectious Diseases › Leprosy Research and Treatment
  • Health Sciences › Medicine › Infectious Diseases › Parasitic Diseases Research and Treatment
Keywords
Leishmania major, IL-10, parasite persistence, latent infection, disease reactivation, CD4+ T cells, CD8+ T cells, interferon-gamma, skin infections, draining lymph nodes, reservoir of infection, C57BL/6 mice
MeSH terms
Animals, Antibodies, Monoclonal, Interferon-gamma, Mice, Inbred C57BL, Skin, CD4-Positive T-Lymphocytes, Interleukin-4, Interleukin-10, Leishmaniasis, Cutaneous, Receptors, Interleukin, Leishmania major, Mice, Knockout, CD8-Positive T-Lymphocytes, Mice, Receptors, Interleukin-10

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