Reduced CD3/TCR complex expression leads to immunosuppression during Plasmodium falciparum malaria.
Inhibition of T cell function is an important pathological feature in malaria. We investigated which T cell population is reduced contributing to immunosuppression. We examined protein and RNA level of various cell receptors, specific for T cells in children having Plasmodium falciparum infection and compared those to healthy children of the same age. We observe reduced levels of cluster of differentiation (CD)3 and T cell receptor (TCR)alphabeta in both RNA and protein expression level. This reduced expression was associated with a collapsed membrane asymmetry as determined by enhanced annexinV binding. Also human leukocyte antigen (HLA)-A,B,C- and HLA-DR-positive cells increasingly bound annexinV. The enhanced binding of annexinV was paralleled by a reduced expression of transcription factors such as T cell transcription factor 7 and GATA binding protein 3, which are involved in the expression of T cell specific genes. Also the expression of the transcription factors major histocompatibility complex class II transactivator and regulatory factor X 5, which are part of the HLA transcription machinery, is reduced during infection. We show that two mechanisms may lead to a suppression of the immune system during malaria: cell damage and reduction of gene expression of the CD3/TCR complex.
Kalmbach
Yvonne
Y
Department of Parasitology, Institute for Tropical Medicine, University of Tübingen, Wilhelmstr. 27, 72074, Tübingen, Germany.
Boldt
Angelica B W
AB
Mordmüller
Benjamin
B
Kombila
Maryvonne
M
Grobusch
Martin P
MP
Kremsner
Peter G
PG
Kun
Jürgen F J
JF
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017252:CD3 Complex / Q000096:biosynthesis*; D002462:Cell Membrane / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007165:Immunosuppression Therapy; D007223:Infant; D016778:Malaria, Falciparum / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis
D017304:Annexin A5; D017252:CD3 Complex; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014157:Transcription Factors