title: Up-regulated S100 calcium binding protein A8 in Plasmodium-infected patients correlates with CD4(+)CD25(+)Foxp3 regulatory T cell generation.
abstract: BACKGROUND
  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.
  
  
  METHODS
  The 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).
  
  
  RESULTS
  A 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.
  
  
  CONCLUSIONS
  Treg 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.
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, 32610, USA. rainlee67@naver.com.
authors.forename: Hyeong-Woo
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Parasitology and Tropical Medicine, Inha Research Institute for Medical Sciences, Inha University School of Medicine, Incheon, 400-712, Republic of Korea. tongsookim@inha.ac.kr.
authors.forename: Tong-Soo
authors.initials: TS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, Jungwon University, Goesan, Chungbuk, 367-805, Republic of Korea. yjkang@jwu.ac.kr.
authors.forename: Yoon-Joong
authors.initials: YJ
authors.lastname: Kang
authors.affiliation: Division of Malaria and Parasitic Disease, Korea National Institute of Health, Osong, 363-951, Republic of Korea. creative-kim@hamail.net.
authors.forename: Jung-Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, 32610, USA. sangwe13@gmail.com.
authors.forename: Sangeun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Division of Arbovirus, Korea National Institute of Health, Osong, 363-951, Republic of Korea. leewonja@gmail.com.
authors.forename: Won-Ja
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Department of Anatomy, College of Korean Medicine, Institute of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea. youngjoos@khu.ac.kr.
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Sohn
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, 32610, USA. rainlee67@naver.com.
authors.forename: Hyeong-Woo
authors.initials: HW
authors.lastname: Lee
mesh_terms: D000328:Adult; D015704:CD4 Antigens / Q000032:analysis; D040501:Calgranulin A / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D057131:Immune Evasion; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D016780:Malaria, Vivax / Q000276:immunology*; D010966:Plasmodium vivax / Q000276:immunology* / Q000502:physiology; D044967:Serum / Q000737:chemistry; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D040501:Calgranulin A; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit