Author(s):
Lombana, Claudia Gonzalez ; Gimblet, Ciara ; Bacellar, Maria Olívia Amado Ramos ; Oliveira, Walker W. ; Passos, Sara ; Carvalho, Lucas Pedreira de ; Goldschmidt, Michael ; Carvalho Filho, Edgar Marcelino de ; Scott, Phillip ; Lombana, Claudia Gonzalez ; Gimblet, Ciara ; Bacellar, Maria Olívia Amado Ramos ; Oliveira, Walker W. ; Passos, Sara ; Carvalho, Lucas Pedreira de ; Goldschmidt, Michael ; Carvalho Filho, Edgar Marcelino de ; Scott, Phillip
Date: 2014
Origin: Oasisbr
Subject(s): Leishmaniasis; Interleukin-17; Interleukin-10; Leishmaniasis cutaneous
Description
p. 1-14
Submitted by Edileide Reis (leyde-landy@hotmail.com) on 2014-12-01T11:23:49Z No. of bitstreams: 1 Claudia Gonzalez Lombana.pdf: 1907722 bytes, checksum: cc9acc0548f3518beac68821242128f2 (MD5)
Approved for entry into archive by Flávia Ferreira (flaviaccf@yahoo.com.br) on 2014-12-01T11:51:48Z (GMT) No. of bitstreams: 1 Claudia Gonzalez Lombana.pdf: 1907722 bytes, checksum: cc9acc0548f3518beac68821242128f2 (MD5)
Made available in DSpace on 2014-12-01T11:51:48Z (GMT). No. of bitstreams: 1 Claudia Gonzalez Lombana.pdf: 1907722 bytes, checksum: cc9acc0548f3518beac68821242128f2 (MD5) Previous issue date: 2013
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.
