Human Intestinal Epithelial Cells Release Antiviral Factors That Inhibit HIV Infection of Macrophages
As a rich source of CD4+ T cells and macrophages, the gastrointestinal (GI) tract is a major target site for HIV infection. The interplay between GI-resident macrophages and intestinal epithelial cells (IECs) constitutes an important element of GI innate immunity against pathogens. In this study, we...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00247/full |
| _version_ | 1818545332140638208 |
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| author | Le Guo Xi-Qiu Xu Li Zhou Run-Hong Zhou Xu Wang Jie-Liang Li Jin-Biao Liu Hang Liu Biao Zhang Wen-Zhe Ho Wen-Zhe Ho |
| author_facet | Le Guo Xi-Qiu Xu Li Zhou Run-Hong Zhou Xu Wang Jie-Liang Li Jin-Biao Liu Hang Liu Biao Zhang Wen-Zhe Ho Wen-Zhe Ho |
| author_sort | Le Guo |
| collection | DOAJ |
| description | As a rich source of CD4+ T cells and macrophages, the gastrointestinal (GI) tract is a major target site for HIV infection. The interplay between GI-resident macrophages and intestinal epithelial cells (IECs) constitutes an important element of GI innate immunity against pathogens. In this study, we investigated whether human IECs have the ability to produce antiviral factors that can inhibit HIV infection of macrophages. We demonstrated that IECs possess functional toll-like receptor 3 (TLR3), the activation of which resulted in induction of key interferon (IFN) regulatory factors (IRF3 and IRF7), IFN-β, IFN-λ, and CC chemokines (MIP-1α, MIP-1β, RANTES), the ligands of HIV entry co-receptor CCR5. In addition, TLR3-activated IECs release exosomes that contained the anti-HIV factors, including IFN-stimulated genes (ISGs: ISG15, ISG56, MxB, OAS-1, GBP5, and Viperin) and HIV restriction miRNAs (miRNA-17, miRNA-20, miRNA-28, miRNA-29 family members, and miRNA-125b). Importantly, treatment of macrophages with supernatant (SN) from the activated IEC cultures inhibited HIV replication. Further studies showed that IEC SN could also induce the expression of antiviral ISGs and cellular HIV restriction factors (Tetherin and APOBEC3G/3F) in HIV-infected macrophages. These findings indicated that IECs might act as an important element in GI innate immunity against HIV infection/replication. |
| first_indexed | 2024-12-12T07:38:55Z |
| format | Article |
| id | doaj.art-bf9bcb1ff9b949cfbc8f1ad59b05fc42 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T07:38:55Z |
| publishDate | 2018-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-bf9bcb1ff9b949cfbc8f1ad59b05fc422022-12-22T00:32:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-02-01910.3389/fimmu.2018.00247291485Human Intestinal Epithelial Cells Release Antiviral Factors That Inhibit HIV Infection of MacrophagesLe Guo0Xi-Qiu Xu1Li Zhou2Run-Hong Zhou3Xu Wang4Jie-Liang Li5Jin-Biao Liu6Hang Liu7Biao Zhang8Wen-Zhe Ho9Wen-Zhe Ho10Wuhan University School of Basic Medical Sciences, Wuhan, ChinaWuhan University School of Basic Medical Sciences, Wuhan, ChinaWuhan University School of Basic Medical Sciences, Wuhan, ChinaWuhan University School of Basic Medical Sciences, Wuhan, ChinaDepartment of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United StatesDepartment of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United StatesWuhan University School of Basic Medical Sciences, Wuhan, ChinaWuhan University School of Basic Medical Sciences, Wuhan, ChinaWuhan University School of Basic Medical Sciences, Wuhan, ChinaWuhan University School of Basic Medical Sciences, Wuhan, ChinaDepartment of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United StatesAs a rich source of CD4+ T cells and macrophages, the gastrointestinal (GI) tract is a major target site for HIV infection. The interplay between GI-resident macrophages and intestinal epithelial cells (IECs) constitutes an important element of GI innate immunity against pathogens. In this study, we investigated whether human IECs have the ability to produce antiviral factors that can inhibit HIV infection of macrophages. We demonstrated that IECs possess functional toll-like receptor 3 (TLR3), the activation of which resulted in induction of key interferon (IFN) regulatory factors (IRF3 and IRF7), IFN-β, IFN-λ, and CC chemokines (MIP-1α, MIP-1β, RANTES), the ligands of HIV entry co-receptor CCR5. In addition, TLR3-activated IECs release exosomes that contained the anti-HIV factors, including IFN-stimulated genes (ISGs: ISG15, ISG56, MxB, OAS-1, GBP5, and Viperin) and HIV restriction miRNAs (miRNA-17, miRNA-20, miRNA-28, miRNA-29 family members, and miRNA-125b). Importantly, treatment of macrophages with supernatant (SN) from the activated IEC cultures inhibited HIV replication. Further studies showed that IEC SN could also induce the expression of antiviral ISGs and cellular HIV restriction factors (Tetherin and APOBEC3G/3F) in HIV-infected macrophages. These findings indicated that IECs might act as an important element in GI innate immunity against HIV infection/replication.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00247/fullhuman intestinal epithelial cellsHIVmacrophagestoll-like receptor 3interferonsIFN-stimulated genes |
| spellingShingle | Le Guo Xi-Qiu Xu Li Zhou Run-Hong Zhou Xu Wang Jie-Liang Li Jin-Biao Liu Hang Liu Biao Zhang Wen-Zhe Ho Wen-Zhe Ho Human Intestinal Epithelial Cells Release Antiviral Factors That Inhibit HIV Infection of Macrophages Frontiers in Immunology human intestinal epithelial cells HIV macrophages toll-like receptor 3 interferons IFN-stimulated genes |
| title | Human Intestinal Epithelial Cells Release Antiviral Factors That Inhibit HIV Infection of Macrophages |
| title_full | Human Intestinal Epithelial Cells Release Antiviral Factors That Inhibit HIV Infection of Macrophages |
| title_fullStr | Human Intestinal Epithelial Cells Release Antiviral Factors That Inhibit HIV Infection of Macrophages |
| title_full_unstemmed | Human Intestinal Epithelial Cells Release Antiviral Factors That Inhibit HIV Infection of Macrophages |
| title_short | Human Intestinal Epithelial Cells Release Antiviral Factors That Inhibit HIV Infection of Macrophages |
| title_sort | human intestinal epithelial cells release antiviral factors that inhibit hiv infection of macrophages |
| topic | human intestinal epithelial cells HIV macrophages toll-like receptor 3 interferons IFN-stimulated genes |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00247/full |
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