Monocyte toll-like receptor 4 expression and LPS-induced cytokine production increase during gestational aging.
Premature newborns are highly susceptible to severe bacterial infections. This is partially due to their immature innate immune system, characterized by decreased neutrophil and monocyte activity as well as by reduced concentrations of complement factors. However, additional mechanisms might be important for innate immunity and are still the subject of considerable debate. The importance of pattern recognition domains such as Toll-like receptors (TLR) has been fully acknowledged within the last few years. Therefore, we investigated age-related monocyte TLR4 expression and lipopolysaccharide-induced cytokine secretion from very low birth weight infants (VLBWI) and from newborns after wk 30 of gestation in comparison to healthy adults. In VLBWI, expression of TLR4 surface protein, detected by flow cytometry, and TLR4-specific mRNA, quantified by real time-PCR, were significantly reduced in comparison to mature infants and to adults. Reduced TLR4 expression was paralleled by significantly diminished ex vivo LPS stimulated IL-1beta, IL-6, and tumor necrosis factor-alpha secretion into whole blood. We conclude that, in VLBWI, the minimized expression of TLR4 contributes to the susceptibility of VLBWI to infections with Gram-negative bacteria due to the lack of cytokines to boost initial immune response.
Förster-Waldl
Elisabeth
E
Department of Pediatrics and Juvenile Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Sadeghi
Kambis
K
Tamandl
Dietmar
D
Gerhold
Bernadette
B
Hallwirth
Ulrike
U
Rohrmeister
Klaudia
K
Hayde
Michael
M
Prusa
Andrea R
AR
Herkner
Kurt
K
Boltz-Nitulescu
George
G
Pollak
Arnold
A
Spittler
Andreas
A
D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005312:Fetal Blood / Q000378:metabolism*; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha