IL-17 mediates immunopathology in the absence of IL-10 following Leishmania major infection.
| Autor: | Claudia Gonzalez-Lombana, Ciara Gimblet, Olivia Bacellar, Walker W Oliveira, Sara Passos, Lucas P Carvalho, Michael Goldschmidt, Edgar M Carvalho, Phillip Scott |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | PLoS Pathogens, Vol 9, Iss 3, p e1003243 (2013) |
| Druh dokumentu: | article |
| ISSN: | 1553-7366 1553-7374 |
| DOI: | 10.1371/journal.ppat.1003243 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
| Externí odkaz: |
|