| First Author | Gonzalez-Lombana C | Year | 2013 |
| Journal | PLoS Pathog | Volume | 9 |
| Issue | 3 | Pages | e1003243 |
| PubMed ID | 23555256 | Mgi Jnum | J:337376 |
| Mgi Id | MGI:6843281 | Doi | 10.1371/journal.ppat.1003243 |
| Citation | Gonzalez-Lombana C, et al. (2013) IL-17 mediates immunopathology in the absence of IL-10 following Leishmania major infection. PLoS Pathog 9(3):e1003243 |
| abstractText | 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-gamma and IL-17 levels were substantially elevated in mice lacking the capacity to respond to IL-10. IFN-gamma promoted an increased infiltration of monocytes, while IL-17 contributed to an increase in neutrophils. Surprisingly, however, we found that IFN-gamma did not contribute to increased pathology, but instead regulated the IL-17 response. Thus, blocking IFN-gamma 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-gamma. 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-1beta, may be a useful approach for controlling immunopathology in leishmaniasis. |
