The role of phagocytosis in IL-8 production by human monocytes in response to lipoproteins on Staphylococcus aureus |
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Authors: | Kang Hee Jung Ha Jeong-Mi Kim Han Sung Lee Haneulnari Kurokawa Kenji Lee Bok Luel |
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Affiliation: | aDept. of Laboratory Medicine, Hallym University College of Medicine, Anyang-si, Gyeonggi-do 431-070, Republic of Korea;bNational Research Lab. of Defense Proteins, College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea |
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Abstract: | Cytokine responses to microbes are triggered by pattern recognition receptors, such as Toll-like receptors (TLRs), which sense pathogen-associated molecular patterns. Cell wall-associated triacylated lipoproteins in Staphylococcus aureus are known to be native TLR2 ligands that mediate host inflammatory responses against S. aureus. However, the mechanism by which these lipidated lipoproteins, which are buried under the thick S. aureus cell wall, work to stimulate TLR2 remains unclear. Heat-killed wild type S. aureus cells activated human monocytic THP-1 cells to produce proinflammatory cytokines, including interleukin (IL)-8, whereas the lipoprotein lipidation-deficient lgt mutant induced less than an eighth of the amount of IL-8 induced by the wild type. IL-8 induction in response to heat-killed S. aureus cells in THP-1 cells was not inhibited by a blocking antibody against cell surface TLR2, suggesting that intracellular TLR2 might be involved in the induction of IL-8 by S. aureus lipoprotein. The relationship between phagocytosis and IL-8 production in THP-1 cells was analyzed on a single-cell level by flow cytometry using fluorescein-labeled S. aureus cells and phycoerythrin-labeled anti-IL-8 antibody. Production of intracellular IL-8 was correlated with phagocytosis of S. aureus cells in THP-1 cells and in human peripheral blood mononuclear cells. Opsonization of S. aureus cells enhanced both the phagocytosis of S. aureus cells and the production of intracellular IL-8 in THP-1 cells. These results suggest that lipidated lipoproteins on S. aureus cells stimulate human monocytes after phagocytosis. |
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Keywords: | Abbreviations: PRR, pattern-recognition receptor TLR, Toll-like receptor IL, interleukin PAMP, pathogen-associated molecular pattern LPS, lipopolysaccharide Lgt, lipoprotein diacylglycerol transferase Lnt, lipoprotein N-acyl transferase Δlgt, lgt gene deletion PBS, phosphate buffered saline PBMC, peripheral blood mononuclear cell FBS, fetal bovine serum TNF, tumor necrotizing factor MOI, multiplicity of infection PE, phycoerythrin MFI, mean fluorescence intensities |
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