Distinct microenvironmental cues stimulate divergent TLR4-mediated signaling pathways in macrophages
Macrophages exhibit a phenotypic plasticity that enables them to orchestrate specific immune responses to distinct threats. The microbial product lipopolysaccharide (LPS) and the extracellular matrix glycoprotein tenascin-C are released during bacterial infection and tissue injury, respectively, and...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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American Association for the Advancement of Science
2016
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| _version_ | 1797081738382409728 |
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| author | Piccinini, AM Zuliani-Alvarez, L Lim, JMP Midwood, KS |
| author_facet | Piccinini, AM Zuliani-Alvarez, L Lim, JMP Midwood, KS |
| author_sort | Piccinini, AM |
| collection | OXFORD |
| description | Macrophages exhibit a phenotypic plasticity that enables them to orchestrate specific immune responses to distinct threats. The microbial product lipopolysaccharide (LPS) and the extracellular matrix glycoprotein tenascin-C are released during bacterial infection and tissue injury, respectively, and both activate Toll-like receptor 4 (TLR4). We found that these two TLR4 ligands stimulated distinct signaling pathways in macrophages, resulting in cells with divergent phenotypes. Although macrophages activated by LPS or tenascin-C displayed some common features, including activation of nuclear factor κB and mitogen-activated protein kinase signaling and cytokine synthesis, each ligand stimulated the production of different subsets of cytokines and generated different phosphoproteomic signatures. Moreover, tenascin-C promoted the generation of macrophages that exhibited increased synthesis and phosphorylation of extracellular matrix components, whereas LPS stimulated the production of macrophages that exhibited an enhanced capacity to degrade the matrix. These data reveal how the activation of one pattern recognition receptor by different microenvironmental cues generates macrophage with distinct phenotypes. |
| first_indexed | 2024-03-07T01:18:13Z |
| format | Journal article |
| id | oxford-uuid:8f715471-256b-452f-8f5b-0966a3b19d37 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:18:13Z |
| publishDate | 2016 |
| publisher | American Association for the Advancement of Science |
| record_format | dspace |
| spelling | oxford-uuid:8f715471-256b-452f-8f5b-0966a3b19d372022-03-26T23:04:19ZDistinct microenvironmental cues stimulate divergent TLR4-mediated signaling pathways in macrophagesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8f715471-256b-452f-8f5b-0966a3b19d37EnglishSymplectic Elements at OxfordAmerican Association for the Advancement of Science2016Piccinini, AMZuliani-Alvarez, LLim, JMPMidwood, KSMacrophages exhibit a phenotypic plasticity that enables them to orchestrate specific immune responses to distinct threats. The microbial product lipopolysaccharide (LPS) and the extracellular matrix glycoprotein tenascin-C are released during bacterial infection and tissue injury, respectively, and both activate Toll-like receptor 4 (TLR4). We found that these two TLR4 ligands stimulated distinct signaling pathways in macrophages, resulting in cells with divergent phenotypes. Although macrophages activated by LPS or tenascin-C displayed some common features, including activation of nuclear factor κB and mitogen-activated protein kinase signaling and cytokine synthesis, each ligand stimulated the production of different subsets of cytokines and generated different phosphoproteomic signatures. Moreover, tenascin-C promoted the generation of macrophages that exhibited increased synthesis and phosphorylation of extracellular matrix components, whereas LPS stimulated the production of macrophages that exhibited an enhanced capacity to degrade the matrix. These data reveal how the activation of one pattern recognition receptor by different microenvironmental cues generates macrophage with distinct phenotypes. |
| spellingShingle | Piccinini, AM Zuliani-Alvarez, L Lim, JMP Midwood, KS Distinct microenvironmental cues stimulate divergent TLR4-mediated signaling pathways in macrophages |
| title | Distinct microenvironmental cues stimulate divergent TLR4-mediated signaling pathways in macrophages |
| title_full | Distinct microenvironmental cues stimulate divergent TLR4-mediated signaling pathways in macrophages |
| title_fullStr | Distinct microenvironmental cues stimulate divergent TLR4-mediated signaling pathways in macrophages |
| title_full_unstemmed | Distinct microenvironmental cues stimulate divergent TLR4-mediated signaling pathways in macrophages |
| title_short | Distinct microenvironmental cues stimulate divergent TLR4-mediated signaling pathways in macrophages |
| title_sort | distinct microenvironmental cues stimulate divergent tlr4 mediated signaling pathways in macrophages |
| work_keys_str_mv | AT piccininiam distinctmicroenvironmentalcuesstimulatedivergenttlr4mediatedsignalingpathwaysinmacrophages AT zulianialvarezl distinctmicroenvironmentalcuesstimulatedivergenttlr4mediatedsignalingpathwaysinmacrophages AT limjmp distinctmicroenvironmentalcuesstimulatedivergenttlr4mediatedsignalingpathwaysinmacrophages AT midwoodks distinctmicroenvironmentalcuesstimulatedivergenttlr4mediatedsignalingpathwaysinmacrophages |