Open AccessIL-17 Mediates Immunopathology in the Absence of IL-10 Following Leishmania major Infection
Author(s) -
Claudia Gonzalez-Lombana,
Ciara Gimblet,
Olı́via Bacellar,
Walker W. Oliveira,
Sara Passos,
Lucas P. Carvalho,
Michael H. Goldschmidt,
Edgar M. Carvalho,
Phillip Scott
Publication year - 2013
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1003243
Subject(s) - immunology , leishmania , leishmaniasis , cutaneous leishmaniasis , immunopathology , leishmania major , interleukin 10 , biology , visceral leishmaniasis , interleukin 17 , leishmania mexicana , cytokine , parasite hosting , world wide web , computer science
Leishmaniasis, resulting from infection with the protozoan parasite Leishmania , consists of a wide spectrum of clinical manifestations, from healing cutaneous lesions to fatal visceral infections. A particularly severe form of cutaneous leishmaniasis, termed mucosal leishmaniasis, exhibits decreased IL-10 levels and an exaggerated inflammatory response that perpetuates the disease. Using a mouse model of leishmaniasis, we investigated what cytokines contribute to increased pathology when IL-10-mediated regulation is absent. Leishmania major infected C57BL/6 mice lacking IL-10 regulation developed larger lesions than controls, but fewer parasites. Both IFN-γ and IL-17 levels were substantially elevated in mice lacking the capacity to respond to IL-10. IFN-γ promoted an increased infiltration of monocytes, while IL-17 contributed to an increase in neutrophils. Surprisingly, however, we found that IFN-γ did not contribute to increased pathology, but instead regulated the IL-17 response. Thus, blocking IFN-γ led to a significant increase in IL-17, neutrophils and disease. Similarly, the production of IL-17 by cells from leishmaniasis patients was also regulated by IL-10 and IFN-γ. Additional studies found that the IL-1 receptor was required for both the IL-17 response and increased pathology. Therefore, we propose that regulating IL-17, possibly by downregulating IL-1β, may be a useful approach for controlling immunopathology in leishmaniasis.