title: Differences in innate cytokine responses between European and African children.
abstract: Although differences in immunological responses between populations have been found in terms of vaccine efficacy, immune responses to infections and prevalence of chronic inflammatory diseases, the mechanisms responsible for these differences are not well understood. Therefore, innate cytokine responses mediated by various classes of pattern-recognition receptors including Toll-like receptors (TLR), C-type lectin receptors (CLRs) and nucleotide-binding oligomerisation domain-like receptors (NLRs) were compared between Dutch (European), semi-urban and rural Gabonese (African) children. Whole blood was stimulated for 24 hours and the pro-inflammatory tumor necrosis factor (TNF) and the anti-inflammatory/regulatory interleukin-10 (IL-10) cytokines in culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA). Gabonese children had a lower pro-inflammatory response to poly(I:C) (TLR3 ligand), but a higher pro-inflammatory response to FSL-1 (TLR2/6 ligand), Pam3 (TLR2/1 ligand) and LPS (TLR4 ligand) compared to Dutch children. Anti-inflammatory responses to Pam3 were also higher in Gabonese children. Non-TLR ligands did not induce substantial cytokine production on their own. Interaction between various TLR and non-TLR receptors was further assessed, but no differences were found between the three populations. In conclusion, using a field applicable assay, significant differences were observed in cytokine responses between European and African children to TLR ligands, but not to non-TLR ligands.
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon; Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany.
authors.forename: Lucja A
authors.initials: LA
authors.lastname: Labuda
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon.
authors.forename: Sanne E
authors.initials: SE
authors.lastname: de Jong
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Lynn
authors.initials: L
authors.lastname: Meurs
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands; Department of Parasitology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Accra, Ghana.
authors.forename: Abena S
authors.initials: AS
authors.lastname: Amoah
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands; Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Immunology Department of the Laboratory of Bacteriology and Virology of Aristide Le Dantec University Hospital, Dakar, Senegal.
authors.forename: Moustapha
authors.initials: M
authors.lastname: Mbow
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon; Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany.
authors.forename: Ulysse
authors.initials: U
authors.lastname: Ateba-Ngoa
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Alwin J
authors.initials: AJ
authors.lastname: van der Ham
authors.affiliation: Department of Dermatology/Allergology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: André C
authors.initials: AC
authors.lastname: Knulst
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Yazdanbakhsh
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon; Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany.
authors.forename: Ayola A
authors.initials: AA
authors.lastname: Adegnika
mesh_terms: D000293:Adolescent; D044383:Black People; D002648:Child; D005260:Female; D005681:Gabon; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology* / Q000502:physiology*; D016753:Interleukin-10 / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D008297:Male; D009426:Netherlands; D051193:Toll-Like Receptors / Q000819:agonists / Q000276:immunology; D044465:White People
chemical_list: C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D051193:Toll-Like Receptors; D016753:Interleukin-10
references.citation: Immunol Rev. 2007 Oct;219:75-87
references.pmid: 17850483
references.citation: Lancet. 1997 Oct 4;350(9083):1015-20
references.pmid: 9329526
references.citation: Eur J Immunol. 2009 May;39(5):1379-86
references.pmid: 19291703
references.citation: Am J Trop Med Hyg. 2001 Nov;65(5):504-9
references.pmid: 11716105
references.citation: Lancet. 1998 Apr 25;351(9111):1225-32
references.pmid: 9643741
references.citation: BMC Syst Biol. 2010 Oct 07;4:137
references.pmid: 20929569
references.citation: Am J Trop Med Hyg. 2001 Nov;65(5):599-602
references.pmid: 11716121
references.citation: PLoS Negl Trop Dis. 2010 Apr 20;4(4):e667
references.pmid: 20422029
references.citation: Nat Immunol. 2012 May 18;13(6):535-42
references.pmid: 22610250
references.citation: Lancet. 1995 Nov 18;346(8986):1339-45
references.pmid: 7475776
references.citation: J Allergy Clin Immunol. 2014 Mar;133(3):818-26.e4
references.pmid: 24290283
references.citation: Pediatr Res. 2008 Dec;64(6):631-6
references.pmid: 18679157
references.citation: Science. 2002 Apr 19;296(5567):490-4
references.pmid: 11964470
references.citation: Lancet. 2001 Feb 24;357(9256):607-8
references.pmid: 11558491
references.citation: Rev Inst Med Trop Sao Paulo. 1972 Nov-Dec;14(6):397-400
references.pmid: 4675644
references.citation: Immunobiology. 2007;212(6):475-90
references.pmid: 17544832
references.citation: Int Arch Allergy Immunol. 2001 Nov;126(3):231-8
references.pmid: 11752881
references.citation: Lancet. 1987 Jun 13;1(8546):1342-5
references.pmid: 2884455
references.citation: J Trop Med. 2012;2012:819512
references.pmid: 22131998
references.citation: Cell Microbiol. 2008 Oct;10(10):2058-66
references.pmid: 18549457
references.citation: Nat Rev Immunol. 2012 Feb 24;12(3):215-25
references.pmid: 22362354
references.citation: Infect Immun. 2004 May;72(5):2598-604
references.pmid: 15102768
references.citation: Curr Opin Allergy Clin Immunol. 2008 Oct;8(5):391-7
references.pmid: 18769190
references.citation: J Allergy Clin Immunol. 2009 Sep;124(3):544-50, 550.e1-2
references.pmid: 19500827
references.citation: Nat Immunol. 2007 Nov;8(11):1179-87
references.pmid: 17952043
references.citation: Cell Host Microbe. 2011 May 19;9(5):355-61
references.pmid: 21575907
references.citation: Allergy. 2009 Oct;64(10):1493-1497
references.pmid: 19385958
references.citation: J Infect Dis. 2009 Mar 15;199(6):795-800
references.pmid: 19434928
references.citation: Eur J Immunol. 2009 Mar;39(3):730-40
references.pmid: 19197942
references.citation: Am J Trop Med Hyg. 1991 Mar;44(3):336-44
references.pmid: 2035755
references.citation: N Engl J Med. 2002 Sep 19;347(12):911-20
references.pmid: 12239261
references.citation: Clin Vaccine Immunol. 2013 Mar;20(3):427-32
references.pmid: 23345580
references.citation: J Infect Dis. 2004 Mar 15;189(6):1044-51
references.pmid: 14999608
references.citation: J Autoimmun. 2005;25 Suppl:74-80
references.pmid: 16278064
references.citation: J Immunol. 2014 Mar 1;192(5):1997-2006
references.pmid: 24563502
references.citation: PLoS One. 2011;6(9):e24393
references.pmid: 21931706
references.citation: J Immunol. 2005 Jul 15;175(2):1170-6
references.pmid: 16002719
references.citation: PLoS Negl Trop Dis. 2008 Apr 16;2(4):e227
references.pmid: 18414649