African trypanosomiasis: naturally occurring regulatory T cells favor trypanotolerance by limiting pathology associated with sustained type 1 inflammation.
Tolerance to African trypanosomes requires the production of IFN-gamma in the early stage of infection that triggers the development of classically activated macrophages controlling parasite growth. However, once the first peak of parasitemia has been controlled, down-regulation of the type 1 immune response has been described. In this study, we have evaluated whether regulatory T cells (Tregs) contribute to the limitation of the immune response occurring during Trypanosoma congolense infection and hereby influence the outcome of the disease in trypanotolerant C57BL/6 host. Our data show that Foxp3+ Tregs originating from the naturally occurring Treg pool expanded in the spleen and the liver of infected mice. These cells produced IL-10 and limited the production of IFN-gamma by CD4+ and CD8+ effector T cells. Tregs also down-regulated classical activation of macrophages resulting in reduced TNF-alpha production. The Treg-mediated suppression of the type 1 inflammatory immune response did not hamper parasite clearance, but was beneficial for the host survival by limiting the tissue damages, including liver injury. Collectively, these data suggest a cardinal role for naturally occurring Tregs in the development of a trypanotolerant phenotype during African trypanosomiasis.
Guilliams
Martin
M
Department of Molecular and Cellular Interactions, Vlaams Instituut voor Biotechnologie, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
Oldenhove
Guillaume
G
Noel
Wim
W
Hérin
Michel
M
Brys
Lea
L
Loi
Patrizia
P
Flamand
Véronique
V
Moser
Muriel
M
De Baetselier
Patrick
P
Beschin
Alain
A
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000032:analysis; D007249:Inflammation / Q000276:immunology / Q000469:parasitology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014348:Trypanosoma congolense / Q000276:immunology*; D014353:Trypanosomiasis, African / Q000276:immunology* / Q000473:pathology
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016753:Interleukin-10; D007371:Interferon-gamma