Expression of toll-like receptors in neonatal sepsis.
Despite recent identification of specific pattern recognition receptors (PRR) for distinct microbial structures, data indicating their relevance in human infectious diseases are limited. We determined the expression levels of the Toll-like receptor (TLR)2 and TLR4 by flow cytometry on granulocytes and monocytes of healthy neonates compared with healthy adults. The basal expression of TLR2 was only slightly lower in neonatal phagocytes, whereas no differences could be detected for TLR4. Analyzing neonates with sepsis, we found an impressive up-regulation of TLR2 on blood phagocytes already at initial presentation of symptoms. Comparison with C-reactive protein, IL-8, and IL-6 suggested that TLR2 expression on monocytes is comparably valuable as an early sepsis marker. TLR2 was differentially regulated during neonatal sepsis, showing a constant up-regulation on monocytes but only a transient increase on granulocytes. Surprisingly, TLR4 showed no remarkable changes. Our results revealed a mild deficiency of TLR2 expression in newborns and demonstrated a differential expression of TLR2 but not TLR4 in the course of neonatal sepsis, which could reflect specific inflammatory responses to distinct pathogens. The definition of TLR expression patterns might open a new field of therapeutic targets for neonatal sepsis.
Viemann
Dorothee
D
Department of Pediatrics, University of Munster, Germany. viemannd@uni-muenster.de
Dubbel
Gabriele
G
Schleifenbaum
Susanne
S
Harms
Erik
E
Sorg
Clemens
C
Roth
Johannes
J
D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism; D018805:Sepsis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000096:biosynthesis* / Q000378:metabolism; D015854:Up-Regulation
D015850:Interleukin-6; D016209:Interleukin-8; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D002097:C-Reactive Protein