title: Toll-like receptors stimulate human neutrophil function.
abstract: The first immune cell to arrive at the site of infection is the neutrophil. Upon arrival, neutrophils quickly initiate microbicidal functions, including the production of antimicrobial products and proinflammatory cytokines that serve to contain infection. This allows the acquired immune system enough time to generate sterilizing immunity and memory. Neutrophils detect the presence of a pathogen through germ line-encoded receptors that recognize microbe-associated molecular patterns. In vertebrates, the best characterized of these receptors are Toll-like receptors (TLRs). We have determined the expression and function of TLRs in freshly isolated human neutrophils. Neutrophils expressed TLR1, 2, 4, 5, 6, 7, 8, 9, and 10-all the TLRs except TLR3. Granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment increased TLR2 and TLR9 expression levels. The agonists of all TLRs expressed in neutrophils triggered or primed cytokine release, superoxide generation, and L-selectin shedding, while inhibiting chemotaxis to interleukin-8 (IL-8) and increasing phagocytosis of opsonized latex beads. The response to the TLR9 agonist nonmethylated CpG-motif-containing DNA (CpG DNA) required GM-CSF pretreatment, which also enhanced the response to the other TLR agonists. Finally, using quantitative polymerase chain reaction (QPCR), we demonstrate a chemokine expression profile that suggests that TLR-stimulated neutrophils recruit innate, but not acquired, immune cells to sites of infection.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, USA.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Hayashi
authors.forename: Terry K
authors.initials: TK
authors.lastname: Means
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
mesh_terms: D048429:Cell Size / Q000276:immunology; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D018899:CpG Islands / Q000235:genetics; D015870:Gene Expression / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D019041:L-Selectin / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013481:Superoxides / Q000378:metabolism; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors
chemical_list: D016209:Interleukin-8; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495344:TLR3 protein, human; C495371:TLR9 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D013481:Superoxides; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor