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Abstract
BackgroundThe pro-inflammatory S100 calcium binding protein A8 (S100A8) is elevated in the serum of patients with Plasmodium falciparum malaria, but its function in Plasmodium vivax malaria is not yet clear. This function was investigated in P. vivax-infected patients in this study.MethodsThe level of S100A8 in the serum was measured with ELISA. Full amino acids of S100A8 were synthesized to verify the functions for maturation of immature dendritic cell (iDC) and evaluation of CD4+CD25+Foxp3+ regulatory T (Treg) generation by mature DC (mDC).ResultsA higher amount of S100A8 was detected in vivax-infected patients (141.2 ± 61.849 ng/ml, n = 40) compared with normal control group (48.1 ± 27.384 ng/ml, n = 40). The level of S100A8 did not coincide with that of anti-malarial antibody measured by indirect fluorescent antibody test (IFAT) using parasite-infected red blood cells as antigen. Programmed death-ligand 1 (PD-L1) was up-regulated on the surface of iDCs following treatment with synthetic S100A8, not with synthetic MSP-1, AMA-1 and CSP, as compared to the expression seen for non-treated iDCs. The addition of red blood cells of infected patients to iDCs also elevated their surface expression of CD86. However, the serum levels of S100A8 decreased with increase in parasitaemia. DCs matured by sera containing S100A8 generated Treg cells from naïve T cells. The ratio of Treg cells generated was inversely proportional to the concentration of S100A8 in sera.ConclusionsTreg cells suppress the activity of cytotoxic T cells, which kill malaria parasites; therefore, the up-regulation of S100A8 in malaria patients may contribute to pathogen immune escape or tolerance.
Highlights
The pro-inflammatory S100 calcium binding protein A8 (S100A8) is elevated in the serum of patients with Plasmodium falciparum malaria, but its function in Plasmodium vivax malaria is not yet clear
The concentrations of S100A8 in 40 malaria patients who were confirmed to be infected with Korean isolates of P. vivax was first measured and compared with those of 40 healthy controls (Fig. 1)
To determine if any correlation existed between S100A8 concentrations and anti-malaria antibody titres, indirect fluorescent antibody test (IFAT) assays using P. vivax-infected red blood cells (RBCs) antigen were used to assess the presence of anti-malaria antibodies in the sera
Summary
The pro-inflammatory S100 calcium binding protein A8 (S100A8) is elevated in the serum of patients with Plasmodium falciparum malaria, but its function in Plasmodium vivax malaria is not yet clear. This function was investigated in P. vivax-infected patients in this study. Malaria parasites are transmitted to the host via bites from anopheline mosquitoes, and proceed to sequentially infect hepatocytes and red blood cells (RBCs) [1]. Malaria parasites become exposed to professional antigen-presenting cells (APCs) of the host immune system, which can regulate the immunological response to facilitate pathogen clearance [3]. Antigen presentation by DCs leads to tolerance by T cell
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