Dataset Information

Beyond Pattern Recognition: TLR2 Promotes Chemotaxis, Cell Adhesion and Migration in THP-1 Cells

ABSTRACT: The interaction between monocytes and endothelial cells in inflammation is central to chemoattraction, adhesion, and transendothelial migration. Key players such as selectins and their ligands, integrins and other adhesion molecules and their function in these processes are well studied. Toll-like receptor 2 (TLR2), expressed on monocytes, is critical for sensing invading pathogens and initiating a rapid and effective immune response. However, the extended role of TLR2 in monocyte adhesion and migration has only been partially elucidated. To address this question, we performed several functional cell-based assays using monocyte-like wild type (WT), TLR2-knock-out (KO) and, TLR2-knock-in (KI) THP-1 cells. We found that TLR2 promotes faster and stronger adhesion of monocytes to the endothelium and a more intense endothelial barrier disruption after endothelial activation. In addition, we performed quantitative mass-spectrometry, STRING protein analysis, and RT-qPCR, which revealed the association of TLR2 with specific integrins, but also uncovered novel proteins affected by TLR2. In conclusion, we could show that unstimulated TLR2 affects cell adhesion, endothelial barrier disruption, migration, and actin polymerization.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Monocyte, Cell Culture

SUBMITTER: Benjamin Neuditschko

LAB HEAD: Franz Herzog

PROVIDER: PXD041819 | Pride | 2023-10-24

REPOSITORIES: Pride

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Publications

Beyond Pattern Recognition: TLR2 Promotes Chemotaxis, Cell Adhesion, and Migration in THP-1 Cells.

Colleselli Katrin K Ebeyer-Masotta Marie M Neuditschko Benjamin B Stierschneider Anna A Pollhammer Christopher C Potocnjak Mia M Hundsberger Harald H Herzog Franz F Wiesner Christoph C

Cells 20230519 10

The interaction between monocytes and endothelial cells in inflammation is central to chemoattraction, adhesion, and transendothelial migration. Key players, such as selectins and their ligands, integrins, and other adhesion molecules, and their functions in these processes are well studied. Toll-like receptor 2 (TLR2), expressed in monocytes, is critical for sensing invading pathogens and initiating a rapid and effective immune response. However, the extended role of TLR2 in monocyte adhesion a ...[more]

PMID: 37408259

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Project description:We have established that human cytomegalovirus (HCMV) infection modulates the biology of target primary blood monocytes, allowing HCMV to use monocytes as 'vehicles' for its systemic spread. HCMV infection of monocytes results in rapid induction of PI(3)K and NF-kB activity. Integrins, which are upstream of the PI(3)K and NF-kB pathways, were shown to be involved in HCMV binding to and entry into fibroblasts, suggesting that receptor-ligand-mediated signaling following viral binding to integrins on monocytes could trigger the functional changes seen in infected monocytes. We now show that integrin engagement and the activation of the integrin/Src-signaling pathway is essential for the induction of HCMV-infected monocyte motility. To investigate how integrin engagement by HCMV triggers monocyte motility, we examined the infected monocyte transcriptome and found that the integrin/Src-signaling pathway regulates the expression of paxillin, which is an important signal transducer in the regulation of actin rearrangement during cell adhesion and movement. Functionally, we observed that paxillin is activated via the integrin/Src-signaling pathway and is required for monocyte motility. Because motility is intimately connected to cellular cytoskeletal organization, a process that is also important in viral entry, we investigated the role paxillin regulation plays in the process of viral entry of monocytes. New results confirmed that HCMV`s ability to enter target monocytes is significantly inhibited in cells deficient in paxillin expression or that had their integrin/Src/paxillin signaling pathway blocked. From our data, HCMV-cell interactions emerge as an essential trigger for the cellular changes that allow for HCMV entry and hematogenous dissemination. Monocytes were mock-infected, HCMV-infected, or pretreated with PP2 inhibitor prior to HCMV infection. There were three samples analyzed per individual replicate. Three replicates are included. comparative studies with a use of the specific Src kinase activity inhibitor

Dataset Information

Beyond Pattern Recognition: TLR2 Promotes Chemotaxis, Cell Adhesion and Migration in THP-1 Cells

Publications

Beyond Pattern Recognition: TLR2 Promotes Chemotaxis, Cell Adhesion, and Migration in THP-1 Cells.

Similar Datasets

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