Cutting edge: impaired Toll-like receptor expression and function in aging.
Toll-like receptors (TLR) are pattern recognition receptors that recognize conserved molecular patterns on microbes and link innate and adaptive immune systems. We investigated whether the enhanced susceptibility to bacterial, yeast, and viral infections and poor adaptive immune responses in aging are a result of diminished expression and function of TLRs. We examined the expression and function of all murine TLRs on macrophages from young and aged mice. Both splenic and activated peritoneal macrophages from aged mice expressed significantly lower levels of all TLRs. Furthermore, macrophages from aged mice secreted significantly lower levels of IL-6 and TNF-alpha when stimulated with known ligands for TLR1 and 2, 2 and 6,TLR3, TLR4, TLR5, and TLR9 when compared with those from young mice. These results support the concept that increased susceptibility to infections and poor adaptive immune responses in aging may be due to the decline in TLR expression and function.
Renshaw
Mary
M
Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Rockwell
Julie
J
Engleman
Carrie
C
Gewirtz
Andrew
A
Katz
Jacqueline
J
Sambhara
Suryaprakash
S
D000375:Aging / Q000276:immunology*; D000818:Animals; D016922:Cellular Senescence / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology; D029721:Drosophila Proteins; D005260:Female; D007113:Immunity, Innate; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology; D013864:Thioglycolates / Q000494:pharmacology; D051194:Toll-Like Receptor 1; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015054:Zymosan / Q000494:pharmacology
C408982:CPG-oligonucleotide; D029721:Drosophila Proteins; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; D013864:Thioglycolates; D051194:Toll-Like Receptor 1; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan