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Microbicidal Phagocytosis of Nucleus Pulposus Cells Against Staphylococcus aureus via the TLR2/MAPKs Signaling Pathway.

ABSTRACT: Intervertebral disc (IVD) is an immune-privileged organ that lacks immunocytes, such as macrophages or neutrophils; therefore, it is unclear how IVD immunological defense against bacterial infection occurs. Here, we demonstrated that nucleus pulposus cells (NPCs), the vital machinery for maintaining the homeostasis of IVD, exerted microbicidal activity against Staphylococcus aureus via induction of phagolysosome formation. Moreover, we found that the Toll-like receptor 2 (TLR2)/mitogen-activated protein kinases (MAPKs) signaling pathway is critical for bacterial phagocytosis and phagolysosome formation of NPCs. These findings demonstrated for the first time that NPCs could function as non-professional phagocytes against S. aureus infection, thereby enhancing antimicrobial defense against bacterial infections in IVDs.

SUBMITTER: Lin Y

PROVIDER: S-EPMC6538773 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Microbicidal Phagocytosis of Nucleus Pulposus Cells Against <i>Staphylococcus aureus</i> via the TLR2/MAPKs Signaling Pathway.

Lin Yazhou Y Cong Hui H Liu Kewei K Jiao Yucheng Y Yuan Ye Y Tang Guoqing G Chen Yong Y Zheng Yuehuan Y Xiao Jiaqi J Li Changwei C Chen Zhe Z Cao Peng P

Frontiers in immunology 20190522

Intervertebral disc (IVD) is an immune-privileged organ that lacks immunocytes, such as macrophages or neutrophils; therefore, it is unclear how IVD immunological defense against bacterial infection occurs. Here, we demonstrated that nucleus pulposus cells (NPCs), the vital machinery for maintaining the homeostasis of IVD, exerted microbicidal activity against <i>Staphylococcus aureus</i> via induction of phagolysosome formation. Moreover, we found that the Toll-like receptor 2 (TLR2)/mitogen-ac ...[more]

PMID: 31178866

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Project description:BackgroundThe mechanisms underlying M2 macrophage polarization induced by nucleus pulposus (NP) cells are unclear. The effects that M2-polarized macrophages have on NP cells are also controversial.MethodsTranscriptome sequencing was performed to detect the gene change profiles between NP cells from ruptured intervertebral disc (IVD) and normal IVD. The main difference on biological activities between the two cell groups were analyzed by GO analysis and KEGG analysis. Virus transduction, flow cytometry, immunofluorescence, RT-PCR, western blot, CCK-8, TUNEL staining, and AO/EB staining were performed to explore the interactions between NP cells and RAW264.7 macrophages. Statistics were performed using SPSS26.Results801 upregulated and 276 downregulated genes were identified in NP cells from ruptured IVD in mouse models. According to GO and KEGG analysis, we found that the differentially expressed genes (DEG) were dominantly enriched in inflammatory response, extracellular matrix degradation, blood vessel morphogenesis, immune effector process, ossification, chemokine signaling pathway, macrophage activation, etc. CX3CL1 was one of the top 20% DEG, and we confirmed that both NP tissue and cells expressed remarkably higher level of CX3CL1 in mouse models (p < 0.001∗). Besides, we further revealed that both the recombinant CX3CL1 and NP cells remarkably induced M2 polarization of RAW264.7 (p < 0.001∗), respectively, while this effect was significantly reversed by si-CX3CL1 or JMS-17-2 (p < 0.001∗). Furthermore, we found that M2 macrophages significantly decreased the apoptosis rate (p < 0.001∗) and the catabolic gene levels (p < 0.001∗) of NP cells, while increased the viability, proliferation as well as the anabolic gene levels of NP cells (p < 0.01∗).ConclusionsVia regulating CX3CL1/CX3CR1 pathway, NP cells can induce the M2 macrophage polarization. M2 polarized macrophages can further promote NP cell viability, proliferation, and anabolism, while inhibit NP cell apoptosis and catabolism.

Dataset Information

Microbicidal Phagocytosis of Nucleus Pulposus Cells Against Staphylococcus aureus via the TLR2/MAPKs Signaling Pathway.

Publications

Microbicidal Phagocytosis of Nucleus Pulposus Cells Against <i>Staphylococcus aureus</i> via the TLR2/MAPKs Signaling Pathway.

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