Responses to Toll-like receptor ligands in children living in areas where schistosome infections are endemic.
To study the effect of repeated challenge of the innate immune system with pathogen-associated molecular patterns, cytokine responses to schistosomal lipids and bacterial lipopolysaccharide (LPS) were analyzed in schoolchildren living in an area in Gabon where schistosomiasis, a helminth infection that is chronic in nature, is endemic. A schistosomal phosphatidylserine (PS) fraction containing the Toll-like receptor (TLR)-2 ligand lyso-PS stimulated the production of interleukin (IL)-8, IL-10, IL-6, and tumor necrosis factor (TNF)-alpha in children without Schistosoma haematobium infection. However, in infected children, the responses to this stimulus were lower, in particular for production of IL-8 and TNF-alpha. Responses to the TLR4 ligand, LPS, followed a similar pattern. In contrast, schistosomal adult worm glycolipids that did not stimulate any of the TLRs tested induced IL-8 and IL-6 responses that were significantly higher in schistosome-infected children than in schistosome-uninfected children. These results indicate that relentless exposure to pathogens can lead to altered responses to TLR ligands.
Department of Parasitology, Leiden University Medical Center, Leiden,The Netherlands.
Desiree
D
van der Kleij
Anita H J
AH
van den Biggelaar
Yvonne C M
YC
Kruize
Kim
K
Retra
Yvonne
Y
Fillie
Marion
M
Schmitz
Peter G
PG
Kremsner
Aloysius G M
AG
Tielens
Maria
M
Yazdanbakhsh
D000293:Adolescent; D002460:Cell Line; D002648:Child; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006017:Glycolipids / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D010718:Phosphatidylserines / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D012553:Schistosomiasis haematobia / Q000276:immunology*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D016207:Cytokines; D006017:Glycolipids; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D010718:Phosphatidylserines; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors