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

Tom Bosschaerts, Yannick Morias, Benoît Stijlemans, Michel Hérin, Chiara Porta, Antonio Sica, Alberto Mantovani, Patrick De Baetselier, Alain Beschin

Research output: Contribution to journalArticle

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-10 flox/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-10 flox/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.

Original languageEnglish
Pages (from-to)3270-3280
Number of pages11
JournalEuropean Journal of Immunology
Volume41
Issue number11
DOIs
Publication statusPublished - Nov 2011

Keywords

  • Inflammation
  • Inflammatory monocytes
  • Liver

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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