دورية أكاديمية
Mucosal T Helper 17 and T Regulatory Cell Homeostasis Correlate with Acute Simian Immunodeficiency Virus Viremia and Responsiveness to Antiretroviral Therapy in Macaques.
العنوان: | Mucosal T Helper 17 and T Regulatory Cell Homeostasis Correlate with Acute Simian Immunodeficiency Virus Viremia and Responsiveness to Antiretroviral Therapy in Macaques. |
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المؤلفون: | O'Connor MA; 1 Department of Microbiology, University of Washington, Seattle, Washington.; 2 Washington National Primate Research Center, Seattle, Washington., Munson PV; 1 Department of Microbiology, University of Washington, Seattle, Washington.; 2 Washington National Primate Research Center, Seattle, Washington., Tunggal HC; 1 Department of Microbiology, University of Washington, Seattle, Washington.; 2 Washington National Primate Research Center, Seattle, Washington., Hajari N; 1 Department of Microbiology, University of Washington, Seattle, Washington.; 2 Washington National Primate Research Center, Seattle, Washington., Lewis TB; 1 Department of Microbiology, University of Washington, Seattle, Washington.; 2 Washington National Primate Research Center, Seattle, Washington., Bratt D; 2 Washington National Primate Research Center, Seattle, Washington., Moats C; 2 Washington National Primate Research Center, Seattle, Washington., Smedley J; 2 Washington National Primate Research Center, Seattle, Washington., Bagley KC; 3 Profectus Biosciences, Inc., Baltimore, Maryland., Mullins JI; 1 Department of Microbiology, University of Washington, Seattle, Washington., Fuller DH; 1 Department of Microbiology, University of Washington, Seattle, Washington.; 2 Washington National Primate Research Center, Seattle, Washington. |
المصدر: | AIDS research and human retroviruses [AIDS Res Hum Retroviruses] 2019 Mar; Vol. 35 (3), pp. 295-305. Date of Electronic Publication: 2019 Jan 02. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: Mary Ann Liebert Country of Publication: United States NLM ID: 8709376 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1931-8405 (Electronic) Linking ISSN: 08892229 NLM ISO Abbreviation: AIDS Res Hum Retroviruses Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Larchmont, NY : Mary Ann Liebert Original Publication: [New York] : Mary Ann Liebert, [c1987- |
مواضيع طبية MeSH: | Anti-Retroviral Agents/*therapeutic use , Homeostasis/*immunology , Simian Acquired Immunodeficiency Syndrome/*drug therapy , Simian Acquired Immunodeficiency Syndrome/*virology , Simian Immunodeficiency Virus/*pathogenicity , T-Lymphocytes, Regulatory/*immunology , Th17 Cells/*immunology , Viremia/*virology, Animals ; Anti-Retroviral Agents/administration & dosage ; Colon/pathology ; Disease Models, Animal ; HIV Infections/immunology ; Intestinal Mucosa/immunology ; Lymph Nodes/immunology ; Macaca mulatta ; Male ; Mesentery ; Monkey Diseases/drug therapy ; T-Lymphocytes, Regulatory/metabolism ; Treatment Outcome ; Viral Load/genetics |
مستخلص: | Depletion of gut T helper 17 (Th17) cells during HIV infection leads to decreased mucosal integrity and increased disease progression. Conversely, T regulatory (Treg) cells may inhibit antiviral responses or immune activation. In HIV elite controllers, a balanced Th17/Treg ratio is maintained in the blood, suggesting a role for these responses in controlling inflammation and viral replication. HIV-infected individuals exhibit a range in responsiveness to combination antiretroviral therapy (cART). Given the link between the Th17/Treg ratio and HIV disease, we reasoned these responses may play a role in cART responsiveness. In this study, we investigated the relationship between the mucosal Th17/Treg ratio to acute simian immunodeficiency virus (SIV) viremia and the response to cART. Nineteen rhesus macaques were infected with highly pathogenic SIVΔB670 virus and cART was initiated 6 weeks postinfection. Mucosal CD4 T cell subsets were assessed by intracellular cytokine staining in the colon and mesenteric lymph nodes. Higher baseline Th17/Treg ratios corresponded with increased acute SIV viremia. Th17/Treg ratios decreased during acute SIV infection and were not restored during cART, and this corresponded to increased gut immune activation (Ki67 + ), markers of microbial translocation (sCD14), and T cell exhaustion (TIGIT + ). Animals that maintained a more balanced mucosal Th17/Treg ratio at the time of cART initiation exhibited a better virological response to cART and maintained higher peripheral CD4 counts. These results suggest mucosal Th17 and Treg homeostasis influences acute viremia and the response to cART, a result that suggests therapeutic interventions that improve the Th17/Treg ratio before or during cART may improve treatment of HIV. |
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معلومات مُعتمدة: | P51 OD011092 United States OD NIH HHS; P51 OD010425 United States OD NIH HHS; T32 AI007140 United States AI NIAID NIH HHS; R44 AI110315 United States AI NIAID NIH HHS; UM1 AI126623 United States AI NIAID NIH HHS; R01 AI104679 United States AI NIAID NIH HHS; P30 AI027757 United States AI NIAID NIH HHS |
فهرسة مساهمة: | Keywords: Th17; Treg; antiretroviral therapy; mucosal immune responses; rhesus macaque; simian immunodeficiency virus |
المشرفين على المادة: | 0 (Anti-Retroviral Agents) |
تواريخ الأحداث: | Date Created: 20181107 Date Completed: 20200226 Latest Revision: 20200309 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC6434588 |
DOI: | 10.1089/AID.2018.0184 |
PMID: | 30398361 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1931-8405 |
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DOI: | 10.1089/AID.2018.0184 |