Trypanosoma brucei brucei infection impairs MHC class II antigen presentation capacity of macrophages.
During African trypanosomiasis, macrophages play a central role in T cell hyporesponsiveness to parasite-related and unrelated antigens. In this study, the ability of macrophages from Trypanosoma b. brucei-infected mice to present exogenous antigens to a major histocompatibility complex (MHC) class II-restricted CD4+ T cell hybridoma was analysed. We demonstrate that the antigen presentation capacity of macrophages from infected mice is markedly reduced as a result of a lower expression of [MHC class II-peptide] complexes on their plasma membrane. This defect did not result from a decreased antigen uptake/catabolism, a reduced MHC class II and intercellular adhesion molecule 1 expression on the surface of macrophages, a decreased affinity of MHC class II molecules for antigenic peptides, a competition between exogenous and parasite antigens, or the generation of inhibitory peptides. Our data indicate that the step resulting in coexpression of processed antigens and MHC class II molecules is affected in T. b. brucei-infected mice. Additionally, macrophages from infected mice secreted IL-10 that in turn contributes to the impairment of T cell activation.
Namangala
B
B
Department of Immunology, Parasitology and Ultrastructure, Flemish Interuniversity Institute for Biotechnology, Free University Brussels (VUB), Paardenstraat 65, B-1640 St Genesius Rode, Belgium.
Brys
L
L
Magez
S
S
De Baetselier
P
P
Beschin
A
A
D000818:Animals; D017951:Antigen Presentation; D002478:Cells, Cultured; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D014346:Trypanosoma brucei brucei; D014353:Trypanosomiasis, African / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D016753:Interleukin-10