Journal
ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS
Volume 56, Issue 1, Pages 41-53Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00005-008-0008-3
Keywords
neutrophils; bacterial DNA; Toll-like receptor 9; apoptosis; inflammation
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Neutrophils are essential for host defense and detect the presence of invading microorganisms through recognition of pathogen-associated molecular patterns. Among these receptors are Toll-like receptors (TLRs). Neutrophils express all known TLRs except for TLR3. TLR9, localized intracellularly, is to date the best characterized sensor for bacterial DNA, containing short sequences of unmethylated CpG motifs, though TLR9-independent intracellular DNA recognition mechanism(s) may also exist. Bacterial DNA has profound impact on neutrophil functions; it promotes neutrophil trafficking in vivo, induces chemokine expression, regulates expression of adhesion molecules, enhances phagocyte activity, and rescues neutrophils from constitutive apoptosis. TLR9 stimulation results in alterations in cellular redox balance, peroxynitrite formation, activation of the mitogen-activated protein kinase, PI3-kinase, and Jun N-terminal kinase pathways and/or nuclear factor kappa B and AP-1. These features identify an important role for bacterial DNA and TLR9 signaling in the regulation of neutrophil functions that are critical for optimal expression as well as for resolution of the inflammatory response.
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