Experimental expansion of the regulatory T cell population increases resistance to African trypanosomiasis.
Inflammatory responses mounted to eliminate parasites can be lethal if not counterbalanced by regulatory responses protecting the host from collateral tissue damage. Here, we show that the maintained inflammation associated with tissue damage, anemia, and reduced survival of Trypanosoma brucei-infected mice correlates with the absence of the expansion of the regulatory T (T(reg)) cell population. Induction of T(reg) cell expansion via CD28 superagonist antibody treatment in these mice down-regulated interferon-gamma production by T cells and tumor necrosis factor-alpha and reactive oxygen species production by classically activated macrophages, triggered the development of alternatively activated macrophages, delayed the onset of liver injury, diminished the anemia burden, and prolonged the survival of infected animals. Thus, triggering the expansion of the T(reg) cell population coupled with the induction of alternatively activated macrophages can restore the balance between pro- and anti-inflammatory signals and thereby limit the pathogenicity of African trypanosomiasis.
Guilliams
Martin
M
Department of Molecular and Cellular Interactions, Vlaams Instituut voor Biotechnologie, Vrije Universiteit Brussel, Brussels, Belgium.
Bosschaerts
Tom
T
Hérin
Michel
M
Hünig
Thomas
T
Loi
Patrizia
P
Flamand
Véronique
V
De Baetselier
Patrick
P
Beschin
Alain
A
D000740:Anemia / Q000276:immunology; D000818:Animals; D000913:Antibodies, Protozoan; D018106:CD28 Antigens / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D007249:Inflammation / Q000378:metabolism; D008099:Liver / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000502:physiology*; D013997:Time Factors; D014346:Trypanosoma brucei brucei / Q000472:pathogenicity; D014348:Trypanosoma congolense / Q000472:pathogenicity; D014353:Trypanosomiasis, African / Q000276:immunology* / Q000469:parasitology
D000913:Antibodies, Protozoan; D018106:CD28 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse