Interferon (IFN) and Cellular Immune Response Evoked in RNA-Pattern Sensing During Infection with Hepatitis C Virus (HCV)
Hepatitis C virus (HCV) infects hepatocytes but not dendritic cells (DCs), but DCs effectively mature in response to HCV-infected hepatocytes. Using gene-disrupted mice and hydrodynamic injection strategy, we found the MAVS pathway to be crucial for induction of type III interferons (IFNs) in respon...
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| Format: | Article |
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MDPI AG
2015-10-01
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| Series: | Sensors |
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| Online Access: | http://www.mdpi.com/1424-8220/15/10/27160 |
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| author | Masato Nakai Hiroyuki Oshiumi Kenji Funami Masaaki Okamoto Misako Matsumoto Tsukasa Seya Naoya Sakamoto |
| author_facet | Masato Nakai Hiroyuki Oshiumi Kenji Funami Masaaki Okamoto Misako Matsumoto Tsukasa Seya Naoya Sakamoto |
| author_sort | Masato Nakai |
| collection | DOAJ |
| description | Hepatitis C virus (HCV) infects hepatocytes but not dendritic cells (DCs), but DCs effectively mature in response to HCV-infected hepatocytes. Using gene-disrupted mice and hydrodynamic injection strategy, we found the MAVS pathway to be crucial for induction of type III interferons (IFNs) in response to HCV in mouse. Human hepatocytes barely express TLR3 under non-infectious states, but frequently express it in HCV infection. Type I and III IFNs are induced upon stimulation with polyI:C, an analog of double-stranded (ds)RNA. Activation of TLR3 and the TICAM-1 pathway, followed by DC-mediated activation of cellular immunity, is augmented during exposure to viral RNA. Although type III IFNs are released from replication-competent human hepatocytes, DC-mediated CTL proliferation and NK cell activation hardly occur in response to the released type III IFNs. Yet, type I IFNs and HCV-infected hepatocytes can induce maturation of DCs in either human or mouse origin. In addition, mouse CD8+ DCs mature in response to HCV-infected hepatocytes unless the TLR3/TICAM-1 pathway is blocked. We found the exosomes containing HCV RNA in the supernatant of the HCV-infected hepatocytes act as a source of TLR3-mediated DC maturation. Here we summarize our view on the mechanism by which DCs mature to induce NK and CTL in a status of HCV infection. |
| first_indexed | 2024-04-13T08:54:30Z |
| format | Article |
| id | doaj.art-567da0ed4bb7473ea4aa724dcfcfb0c5 |
| institution | Directory Open Access Journal |
| issn | 1424-8220 |
| language | English |
| last_indexed | 2024-04-13T08:54:30Z |
| publishDate | 2015-10-01 |
| publisher | MDPI AG |
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| series | Sensors |
| spelling | doaj.art-567da0ed4bb7473ea4aa724dcfcfb0c52022-12-22T02:53:22ZengMDPI AGSensors1424-82202015-10-011510271602717310.3390/s151027160s151027160Interferon (IFN) and Cellular Immune Response Evoked in RNA-Pattern Sensing During Infection with Hepatitis C Virus (HCV)Masato Nakai0Hiroyuki Oshiumi1Kenji Funami2Masaaki Okamoto3Misako Matsumoto4Tsukasa Seya5Naoya Sakamoto6Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060-8638, JapanDepartment of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060-8638, JapanDepartment of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060-8638, JapanDepartment of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060-8638, JapanDepartment of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060-8638, JapanDepartment of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060-8638, JapanDepartment of Gastroenterology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo 060-8638, JapanHepatitis C virus (HCV) infects hepatocytes but not dendritic cells (DCs), but DCs effectively mature in response to HCV-infected hepatocytes. Using gene-disrupted mice and hydrodynamic injection strategy, we found the MAVS pathway to be crucial for induction of type III interferons (IFNs) in response to HCV in mouse. Human hepatocytes barely express TLR3 under non-infectious states, but frequently express it in HCV infection. Type I and III IFNs are induced upon stimulation with polyI:C, an analog of double-stranded (ds)RNA. Activation of TLR3 and the TICAM-1 pathway, followed by DC-mediated activation of cellular immunity, is augmented during exposure to viral RNA. Although type III IFNs are released from replication-competent human hepatocytes, DC-mediated CTL proliferation and NK cell activation hardly occur in response to the released type III IFNs. Yet, type I IFNs and HCV-infected hepatocytes can induce maturation of DCs in either human or mouse origin. In addition, mouse CD8+ DCs mature in response to HCV-infected hepatocytes unless the TLR3/TICAM-1 pathway is blocked. We found the exosomes containing HCV RNA in the supernatant of the HCV-infected hepatocytes act as a source of TLR3-mediated DC maturation. Here we summarize our view on the mechanism by which DCs mature to induce NK and CTL in a status of HCV infection.http://www.mdpi.com/1424-8220/15/10/27160Hepatitis C virus (HCV)interferon (IFN)-lambdadendritic cells (DCs)Toll-like receptor 3 (TLR3)natural killer (NK) cellcytotoxic T lymphocyte (CTL) |
| spellingShingle | Masato Nakai Hiroyuki Oshiumi Kenji Funami Masaaki Okamoto Misako Matsumoto Tsukasa Seya Naoya Sakamoto Interferon (IFN) and Cellular Immune Response Evoked in RNA-Pattern Sensing During Infection with Hepatitis C Virus (HCV) Sensors Hepatitis C virus (HCV) interferon (IFN)-lambda dendritic cells (DCs) Toll-like receptor 3 (TLR3) natural killer (NK) cell cytotoxic T lymphocyte (CTL) |
| title | Interferon (IFN) and Cellular Immune Response Evoked in RNA-Pattern Sensing During Infection with Hepatitis C Virus (HCV) |
| title_full | Interferon (IFN) and Cellular Immune Response Evoked in RNA-Pattern Sensing During Infection with Hepatitis C Virus (HCV) |
| title_fullStr | Interferon (IFN) and Cellular Immune Response Evoked in RNA-Pattern Sensing During Infection with Hepatitis C Virus (HCV) |
| title_full_unstemmed | Interferon (IFN) and Cellular Immune Response Evoked in RNA-Pattern Sensing During Infection with Hepatitis C Virus (HCV) |
| title_short | Interferon (IFN) and Cellular Immune Response Evoked in RNA-Pattern Sensing During Infection with Hepatitis C Virus (HCV) |
| title_sort | interferon ifn and cellular immune response evoked in rna pattern sensing during infection with hepatitis c virus hcv |
| topic | Hepatitis C virus (HCV) interferon (IFN)-lambda dendritic cells (DCs) Toll-like receptor 3 (TLR3) natural killer (NK) cell cytotoxic T lymphocyte (CTL) |
| url | http://www.mdpi.com/1424-8220/15/10/27160 |
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