Lipoproteins from Staphylococcus aureus Drive Neutrophil Extracellular Trap Formation in a TLR2/1- and PAD-Dependent Manner.
Lipoproteins from Staphylococcus aureus Drive Neutrophil Extracellular Trap Formation in a TLR2/1- and PAD-Dependent Manner.
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DOI：
10.4049/jimmunol.2100283
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发表时间：
2021-08-01
期刊：
影响因子：
--
通讯作者：
Moreland JG
中科院分区：
文献类型：
--
作者：
Hook JS;Patel PA;O'Malley A;Xie L;Kavanaugh JS;Horswill AR;Moreland JG
Neutrophils, polymorphonuclear (PMN) leukocytes, play a critical role in the innate immune response to Staphylococcus aureus, a pathogen that continues to be associated with significant morbidity and mortality. Neutrophil extracellular trap (NET) formation is involved in ensnaring and killing of S. aureus, but this host-pathogen interaction also leads to host tissue damage. Importantly, NET components including neutrophil proteases are under consideration as therapeutic targets in a variety of disease processes. Although S. aureus lipoproteins are recognized to activate cells via toll-like receptors, specific mechanisms of interaction with neutrophils are poorly delineated. We hypothesized that a lipoprotein-containing cell membrane preparation from methicillin resistant S. aureus (MRSA-CMP) would elicit PMN activation including NET formation. We investigated MRSA-CMP-elicited NET formation, regulated elastase release, and IL-8 production in human neutrophils. We studied PMN from healthy donors with or without a common SNP in TLR1, previously demonstrated to impact TLR2/1 signaling, and utilized CMP from both WT MRSA and a mutant lacking palmitoylated lipoproteins (lgt). MRSA-CMP elicited NET formation, elastase release, and IL-8 production in a lipoprotein-dependent manner. TLR2/1 signaling was involved in NET formation and IL-8 production, but not elastase release suggesting that MRSA-CMP-elicited elastase release is not mediated by tri-acylated lipoproteins. MRSA-CMP also primed neutrophils for enhanced NET formation in response to a subsequent stimulus. MRSA-CMP-elicited NET formation did not require Nox2-derived ROS and was partially dependent on the activity of peptidyl arginine deiminase (PAD). In conclusion, lipoproteins from S. aureus mediate NET formation via TLR2/1 with clear implications for patients with sepsis.
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