title: Human immune responses to Plasmodium falciparum infection: molecular evidence for a suboptimal THαβ and TH17 bias over ideal and effective traditional TH1 immune response.
abstract: BACKGROUND
  Using microarray analysis, this study showed up-regulation of toll-like receptors 1, 2, 4, 7, 8, NF-κB, TNF, p38-MAPK, and MHC molecules in human peripheral blood mononuclear cells following infection with Plasmodium falciparum.
  
  
  METHODS
  This analysis reports herein further studies based on time-course microarray analysis with focus on malaria-induced host immune response.
  
  
  RESULTS
  The results show that in early malaria, selected immune response-related genes were up-regulated including α β and γ interferon-related genes, as well as genes of IL-15, CD36, chemokines (CXCL10, CCL2, S100A8/9, CXCL9, and CXCL11), TRAIL and IgG Fc receptors. During acute febrile malaria, up-regulated genes included α β and γ interferon-related genes, IL-8, IL-1b IL-10 downstream genes, TGFB1, oncostatin-M, chemokines, IgG Fc receptors, ADCC signalling, complement-related genes, granzymes, NK cell killer/inhibitory receptors and Fas antigen. During recovery, genes for NK receptors and granzymes/perforin were up-regulated. When viewed in terms of immune response type, malaria infection appeared to induce a mixed TH1 response, in which α and β interferon-driven responses appear to predominate over the more classic IL-12 driven pathway. In addition, TH17 pathway also appears to play a significant role in the immune response to P. falciparum. Gene markers of TH17 (neutrophil-related genes, TGFB1 and IL-6 family (oncostatin-M)) and THαβ (IFN-γ and NK cytotoxicity and ADCC gene) immune response were up-regulated. Initiation of THαβ immune response was associated with an IFN-αβ response, which ultimately resulted in moderate-mild IFN-γ achieved via a pathway different from the more classic IL-12 TH1 pattern.
  
  
  CONCLUSIONS
  Based on these observations, this study speculates that in P. falciparum infection, THαβ/TH17 immune response may predominate over ideal TH1 response.
authors.affiliation: Department of International Health, Johns Hopkins University School of Public Health, Baltimore, MD 21205, USA. lukluk73_2006@yahoo.com.tw.
authors.forename: Wan-Chung
authors.initials: WC
authors.lastname: Hu
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002163:Cameroon; D002478:Cells, Cultured; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology; D008875:Middle Aged; D018448:Models, Immunological; D020411:Oligonucleotide Array Sequence Analysis; D010963:Plasmodium falciparum / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines