| Autor: |
Tom Bosschaerts, Yannick Morias, Benoit Stijlemans, Michel Herin, Chiara Porta, Antonio Sica, Alberto Mantovani, Patrick De Baetselier, Beschin Alain |
| Přispěvatelé: |
Cellular and Molecular Immunology, Department of Bio-engineering Sciences |
| Předmět: |
|
| Zdroj: |
Vrije Universiteit Brussel |
| Popis: |
A balance between parasite elimination and control of infection-associated pathogenicity is crucial for resistance to African trypanosomiasis. By producing TNF and NO, CD11b(+) myeloid cells with a classical activation status (M1) contribute to parasitemia control in experimental Trypanosoma congolense infection in resistant C57BL/6 mice. However, in these mice, IL-10 is required to regulate M1-associated inflammation, avoiding tissue/liver damage and ensuring prolonged survival. In an effort to dissect the mechanisms behind the anti-inflammatory activity of IL-10 in T. congolense infected C57BL/6 mice, we show using antibody blocking IL-10 receptor that IL-10 impairs the accumulation and M1 activation in the liver of TNF/iNOS producing CD11b(+) Ly6C(+) cells. Using infected IL-10(flox/flox) LysM-Cre(+/+) mice, we show that myeloid cell-derived IL-10 limits M1 activation of CD11b(+) Ly6C(+) cells specifically at the level of TNF production. Moreover, higher production of TNF in infected IL-10(flox/flox) LysM-Cre(+/+) mice associated with reduced nuclear accumulation of the NF-kB p50 subunit in CD11b(+) M1 cells. Furthermore, in infected p50 mice, TNF production by CD11b(+) Ly6C(+) cells and liver injury increased. These data suggest that preferential nuclear accumulation of p50 represents an IL-10-dependent anti-inflammatory mechanism in M1-type CD11b(+) myeloid cells that regulates the production of pathogenic TNF during T. congolense infection in resistant C57BL/6 mice. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
