CA-MRSA infections are often caused by strains encoding PVL, which can cause lysis of PMNs and other myeloid cells in vitro, a function considered widely as the primary means by which PVL might contribute to disease. However, at sublytic concentrations, PVL can function as a PMN agonist. To better understand this phenomenon, we investigated the ability of PVL to alter human PMN function. PMNs exposed to PVL had enhanced capacity to produce O-2 (-) in response to fMLF, but unlike priming by LPS, this response did not require TLR signal transduction. On the other hand, there was subcellular redistribution of NADPH oxidase components in PMNs following exposure of these cells to PVL-a finding consistent with priming. Importantly, PMNs primed with PVL had an enhanced ability to bind/ ingest and kill Staphylococcus aureus. Priming of PMNs with other agonists, such as IL-8 or GM-CSF, altered the ability of PVL to cause formation of pores in the plasma membranes of these cells. Microarray analysis revealed significant changes in the human PMN transcriptome following exposure to PVL, including up-regulation of molecules that regulate the inflammatory re- sponse. Consistent with the microarray data, mediators of the inflammatory response were released from PMNs after stimulation with PVL. We conclude that exposure of human PMNs to sublytic concentrations of PVL elicits a proinflammatory response that is regulated in part at the level of gene expression. We propose that PVL-mediated priming of PMNs enhances the host innate immune response. J. Leukoc. Biol. 92: 361-374; 2012.
机构:
Univ Tunis El Manar, Fac Med Tunis, Lab Rech Resistance Antimicrobiens, Tunis, TunisiaUniv Tunis El Manar, Fac Med Tunis, Lab Rech Resistance Antimicrobiens, Tunis, Tunisia
Mariem, Ben Jomaa-Jemili
Ito, Teruyo
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Juntendo Univ, Dept Infect Control Sci, Tokyo, Japan
Juntendo Univ, Dept Bacteriol, Tokyo, JapanUniv Tunis El Manar, Fac Med Tunis, Lab Rech Resistance Antimicrobiens, Tunis, Tunisia
Ito, Teruyo
Zhang, Meng
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Juntendo Univ, Dept Infect Control Sci, Tokyo, JapanUniv Tunis El Manar, Fac Med Tunis, Lab Rech Resistance Antimicrobiens, Tunis, Tunisia
Zhang, Meng
Jin, Jingxun
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Juntendo Univ, Dept Infect Control Sci, Tokyo, JapanUniv Tunis El Manar, Fac Med Tunis, Lab Rech Resistance Antimicrobiens, Tunis, Tunisia
Jin, Jingxun
Li, Shanshuang
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Juntendo Univ, Dept Infect Control Sci, Tokyo, JapanUniv Tunis El Manar, Fac Med Tunis, Lab Rech Resistance Antimicrobiens, Tunis, Tunisia
Li, Shanshuang
Ilhem, Boutiba-Ben Boubaker
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Univ Tunis El Manar, Fac Med Tunis, Lab Rech Resistance Antimicrobiens, Tunis, Tunisia
Charles Nicolle Hosp Tunis, Dept Microbiol, Tunis, TunisiaUniv Tunis El Manar, Fac Med Tunis, Lab Rech Resistance Antimicrobiens, Tunis, Tunisia
Ilhem, Boutiba-Ben Boubaker
Adnan, Hammami
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Habib Borguiba Hosp Sfax, Dept Bacteriol, Tunis, TunisiaUniv Tunis El Manar, Fac Med Tunis, Lab Rech Resistance Antimicrobiens, Tunis, Tunisia
Adnan, Hammami
Han, Xiao
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Juntendo Univ, Dept Infect Control Sci, Tokyo, JapanUniv Tunis El Manar, Fac Med Tunis, Lab Rech Resistance Antimicrobiens, Tunis, Tunisia
Han, Xiao
Hiramatsu, Keiichi
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Juntendo Univ, Dept Infect Control Sci, Tokyo, Japan
Juntendo Univ, Dept Bacteriol, Tokyo, JapanUniv Tunis El Manar, Fac Med Tunis, Lab Rech Resistance Antimicrobiens, Tunis, Tunisia
机构:
Near East Univ, Dept Med Microbiol & Clin Microbiol, Fac Med, Near East Blvd, CY-99138 Nicosia, CyprusNear East Univ, Dept Med Microbiol & Clin Microbiol, Fac Med, Near East Blvd, CY-99138 Nicosia, Cyprus
Amin, Danyar Hameed M.
Guler, Emrah
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Near East Univ, Dept Med Microbiol & Clin Microbiol, Fac Med, Near East Blvd, CY-99138 Nicosia, CyprusNear East Univ, Dept Med Microbiol & Clin Microbiol, Fac Med, Near East Blvd, CY-99138 Nicosia, Cyprus
Guler, Emrah
Baddal, Buket
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Near East Univ, Dept Med Microbiol & Clin Microbiol, Fac Med, Near East Blvd, CY-99138 Nicosia, Cyprus
Near East Univ, DESAM Inst, Microbial Pathogenesis Res Grp, CY-99138 Nicosia, CyprusNear East Univ, Dept Med Microbiol & Clin Microbiol, Fac Med, Near East Blvd, CY-99138 Nicosia, Cyprus