Nociceptors Boost the Resolution of Fungal Osteoinflammation via the TRP Channel-CGRP-Jdp2 Axis
Candida albicans can enter skeletal tissue through a skin wound in an immunocompromised host or by contamination during orthopedic surgery. Such Candida osteomyelitis is accompanied by severe pain and bone destruction. It is established that nociceptor innervation occurs in skin and bone, but the me...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-06-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717307787 |
| _version_ | 1819168778714349568 |
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| author | Kenta Maruyama Yasunori Takayama Takeshi Kondo Ken-ichi Ishibashi Bikash Ranjan Sahoo Hisashi Kanemaru Yutaro Kumagai Mikaël M. Martino Hiroki Tanaka Naohito Ohno Yoichiro Iwakura Naoki Takemura Makoto Tominaga Shizuo Akira |
| author_facet | Kenta Maruyama Yasunori Takayama Takeshi Kondo Ken-ichi Ishibashi Bikash Ranjan Sahoo Hisashi Kanemaru Yutaro Kumagai Mikaël M. Martino Hiroki Tanaka Naohito Ohno Yoichiro Iwakura Naoki Takemura Makoto Tominaga Shizuo Akira |
| author_sort | Kenta Maruyama |
| collection | DOAJ |
| description | Candida albicans can enter skeletal tissue through a skin wound in an immunocompromised host or by contamination during orthopedic surgery. Such Candida osteomyelitis is accompanied by severe pain and bone destruction. It is established that nociceptor innervation occurs in skin and bone, but the mechanisms of nociceptive modulation in fungal inflammation remain unclear. In this study, we show that C. albicans stimulates Nav1.8-positive nociceptors via the β-glucan receptor Dectin-1 to induce calcitonin gene-related peptide (CGRP). This induction of CGRP is independent of Bcl-10 or Malt-1 but dependent on transient receptor potential cation channel subfamily V member 1 (TRPV1)/transient receptor potential cation channel subfamily A member 1 (TRPA1) ion channels. Hindpaw β-glucan injection after Nav1.8-positive nociceptor ablation or in TRPV1/TRPA1 deficiency showed dramatically increased osteoinflammation accompanied by impaired CGRP production. Strikingly, CGRP suppressed β-glucan-induced inflammation and osteoclast multinucleation via direct suppression of nuclear factor-κB (NF-κB) p65 by the transcriptional repressor Jdp2 and inhibition of actin polymerization, respectively. These findings clearly suggest a role for Dectin-1-mediated sensocrine pathways in the resolution of fungal osteoinflammation. |
| first_indexed | 2024-12-22T19:09:01Z |
| format | Article |
| id | doaj.art-1d2bc973c974426cb9cc52333f235fa0 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-22T19:09:01Z |
| publishDate | 2017-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-1d2bc973c974426cb9cc52333f235fa02022-12-21T18:15:44ZengElsevierCell Reports2211-12472017-06-0119132730274210.1016/j.celrep.2017.06.002Nociceptors Boost the Resolution of Fungal Osteoinflammation via the TRP Channel-CGRP-Jdp2 AxisKenta Maruyama0Yasunori Takayama1Takeshi Kondo2Ken-ichi Ishibashi3Bikash Ranjan Sahoo4Hisashi Kanemaru5Yutaro Kumagai6Mikaël M. Martino7Hiroki Tanaka8Naohito Ohno9Yoichiro Iwakura10Naoki Takemura11Makoto Tominaga12Shizuo Akira13Laboratory of Host Defense, WPI Immunology Frontier Research Center (IFReC), Osaka University, Osaka 565-0871, JapanDivision of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Aichi 444-8787, JapanLaboratory of Host Defense, WPI Immunology Frontier Research Center (IFReC), Osaka University, Osaka 565-0871, JapanLaboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, JapanLaboratory of Host Defense, WPI Immunology Frontier Research Center (IFReC), Osaka University, Osaka 565-0871, JapanLaboratory of Host Defense, WPI Immunology Frontier Research Center (IFReC), Osaka University, Osaka 565-0871, JapanLaboratory of Host Defense, WPI Immunology Frontier Research Center (IFReC), Osaka University, Osaka 565-0871, JapanLaboratory of Host Defense, WPI Immunology Frontier Research Center (IFReC), Osaka University, Osaka 565-0871, JapanLaboratory of Host Defense, WPI Immunology Frontier Research Center (IFReC), Osaka University, Osaka 565-0871, JapanLaboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, JapanResearch Institute for Biomedical Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278-0022, JapanDepartment of Mucosal Immunology, School of Medicine, Chiba University, Chiba 260-8670, JapanDivision of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institute for Physiological Sciences, National Institutes of Natural Sciences, Aichi 444-8787, JapanLaboratory of Host Defense, WPI Immunology Frontier Research Center (IFReC), Osaka University, Osaka 565-0871, JapanCandida albicans can enter skeletal tissue through a skin wound in an immunocompromised host or by contamination during orthopedic surgery. Such Candida osteomyelitis is accompanied by severe pain and bone destruction. It is established that nociceptor innervation occurs in skin and bone, but the mechanisms of nociceptive modulation in fungal inflammation remain unclear. In this study, we show that C. albicans stimulates Nav1.8-positive nociceptors via the β-glucan receptor Dectin-1 to induce calcitonin gene-related peptide (CGRP). This induction of CGRP is independent of Bcl-10 or Malt-1 but dependent on transient receptor potential cation channel subfamily V member 1 (TRPV1)/transient receptor potential cation channel subfamily A member 1 (TRPA1) ion channels. Hindpaw β-glucan injection after Nav1.8-positive nociceptor ablation or in TRPV1/TRPA1 deficiency showed dramatically increased osteoinflammation accompanied by impaired CGRP production. Strikingly, CGRP suppressed β-glucan-induced inflammation and osteoclast multinucleation via direct suppression of nuclear factor-κB (NF-κB) p65 by the transcriptional repressor Jdp2 and inhibition of actin polymerization, respectively. These findings clearly suggest a role for Dectin-1-mediated sensocrine pathways in the resolution of fungal osteoinflammation.http://www.sciencedirect.com/science/article/pii/S2211124717307787Candida albicansβ-glucanTRPV1TRPA1osteoclastJdp2NF-κB |
| spellingShingle | Kenta Maruyama Yasunori Takayama Takeshi Kondo Ken-ichi Ishibashi Bikash Ranjan Sahoo Hisashi Kanemaru Yutaro Kumagai Mikaël M. Martino Hiroki Tanaka Naohito Ohno Yoichiro Iwakura Naoki Takemura Makoto Tominaga Shizuo Akira Nociceptors Boost the Resolution of Fungal Osteoinflammation via the TRP Channel-CGRP-Jdp2 Axis Cell Reports Candida albicans β-glucan TRPV1 TRPA1 osteoclast Jdp2 NF-κB |
| title | Nociceptors Boost the Resolution of Fungal Osteoinflammation via the TRP Channel-CGRP-Jdp2 Axis |
| title_full | Nociceptors Boost the Resolution of Fungal Osteoinflammation via the TRP Channel-CGRP-Jdp2 Axis |
| title_fullStr | Nociceptors Boost the Resolution of Fungal Osteoinflammation via the TRP Channel-CGRP-Jdp2 Axis |
| title_full_unstemmed | Nociceptors Boost the Resolution of Fungal Osteoinflammation via the TRP Channel-CGRP-Jdp2 Axis |
| title_short | Nociceptors Boost the Resolution of Fungal Osteoinflammation via the TRP Channel-CGRP-Jdp2 Axis |
| title_sort | nociceptors boost the resolution of fungal osteoinflammation via the trp channel cgrp jdp2 axis |
| topic | Candida albicans β-glucan TRPV1 TRPA1 osteoclast Jdp2 NF-κB |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717307787 |
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