We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
IL-10 limits production of pathogenic TNF by M1 myeloid cells through induction of nuclear NF-κB p50 member in Trypanosoma congolense infection-resistant C57BL/6 mice.
- Authors
Bosschaerts, Tom; Morias, Yannick; Stijlemans, Benoît; Hérin, Michel; Porta, Chiara; Sica, Antonio; Mantovani, Alberto; De Baetselier, Patrick; Beschin, Alain
- Abstract
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 an antibody blocking the IL-10 receptor, that IL-10 impairs the accumulation and M1 activation of TNF/iNOS-producing CD11b+Ly6C+ cells in the liver. Using infected IL-10flox/floxLysM-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-10flox/floxLysM-Cre+/+ mice is associated with reduced nuclear accumulation of the NF-κB p50 subunit in CD11b+ M1 cells. Furthermore, in infected p50−/− mice, TNF production by CD11b+Ly6C+ cells and liver injury increases. 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.
- Publication
European Journal of Immunology, 2011, Vol 41, Issue 11, p3270
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201041307