| Autor: |
Vivarini Ade C; Laboratório de Parasitologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, RJ, Brazil., Pereira Rde M, Teixeira KL, Calegari-Silva TC, Bellio M, Laurenti MD, Corbett CE, Gomes CM, Soares RP, Silva AM, Silveira FT, Lopes UG |
| Jazyk: |
angličtina |
| Zdroj: |
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2011 Dec; Vol. 25 (12), pp. 4162-73. Date of Electronic Publication: 2011 Aug 16. |
| DOI: |
10.1096/fj.11-185165 |
| Abstrakt: |
We investigated the type I interferon (IFN-1)/PKR axis in the outcome of the Leishmania (Leishmania) amazonensis infection, along with the underlying mechanisms that trigger and sustain this signaling pathway. Reporter assays of cell extracts from RAW-264.7 macrophages infected with L. (L.) amazonensis or HEK-293T cells cotransfected with TLR2 and PKR promoter constructions were employed. Primary macrophages of TLR2-knockout (KO) or IFNR-KO mice were infected, and the levels of PKR, IFN-1, and superoxide dismutase 1 (SOD1) transcript levels were investigated and compared. Immunohistochemical analysis of human biopsy lesions was evaluated for IFN-1 and PKR-positive cells. Leishmania infection increased the expression of PKR and IFN-β on induction of PKR-promoter activity. The observed effects required the engagement of TLR2. TLR2-KO macrophages expressed low IFN-β and PKR levels postinfection with a reduced parasite load. We also revealed the requirement of PKR signaling for Leishmania-induced IFN-1 expression, responsible for sustaining PKR expression and enhancing infection. Moreover, during infection, SOD1 transcripts increased and were also enhanced when IFN-1 was added to the cultures. Remarkably, SOD1 expression was abrogated in infected, dominant-negative PKR-expressing cells. Finally, lesions of patients with anergic diffuse cutaneous leishmaniasis exhibited higher levels of PKR/IFN-1-expressing cells compared to those with single cutaneous leishmaniasis. In summary, we demonstrated the mechanisms and relevance of the IFN-1/PKR axis in the Leishmania infection. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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