دورية أكاديمية
Indoleamine-2,3-dioxygenase inhibition improves immunity and is safe for concurrent use with cART during Mtb/SIV coinfection.
| العنوان: | Indoleamine-2,3-dioxygenase inhibition improves immunity and is safe for concurrent use with cART during Mtb/SIV coinfection. |
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| المؤلفون: | Singh B, Sharan R, Ravichandran G, Escobedo R, Shivanna V, Dick EJ Jr, Hall-Ursone S, Arora G, Alvarez X, Singh DK, Kaushal D, Mehra S |
| المصدر: | JCI insight [JCI Insight] 2024 Jul 02; Vol. 9 (15). Date of Electronic Publication: 2024 Jul 02. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]- |
| مواضيع طبية MeSH: | Indoleamine-Pyrrole 2,3,-Dioxygenase*/antagonists & inhibitors , Indoleamine-Pyrrole 2,3,-Dioxygenase*/metabolism , Simian Acquired Immunodeficiency Syndrome*/immunology , Simian Acquired Immunodeficiency Syndrome*/drug therapy , Coinfection*/drug therapy , Coinfection*/immunology , Mycobacterium tuberculosis* , Tryptophan*/metabolism , Tryptophan*/analogs & derivatives , Macaca mulatta*, Animals ; Tuberculosis/immunology ; Tuberculosis/drug therapy ; Simian Immunodeficiency Virus/immunology ; Disease Models, Animal ; CD8-Positive T-Lymphocytes/immunology ; HIV Infections/drug therapy ; HIV Infections/immunology ; HIV Infections/complications ; Anti-Retroviral Agents/therapeutic use ; Anti-Retroviral Agents/pharmacology ; Male ; Lung/immunology ; Lung/pathology ; Humans ; CD4-Positive T-Lymphocytes/immunology |
| مستخلص: | Chronic immune activation promotes tuberculosis (TB) reactivation in the macaque Mycobacterium tuberculosis (M. tuberculosis)/SIV coinfection model. Initiating combinatorial antiretroviral therapy (cART) early lowers the risk of TB reactivation, but immune activation persists. Studies of host-directed therapeutics (HDTs) that mitigate immune activation are, therefore, required. Indoleamine 2,3, dioxygenase (IDO), a potent immunosuppressor, is one of the most abundantly induced proteins in NHP and human TB granulomas. Inhibition of IDO improves immune responses in the lung, leading to better control of TB, including adjunctive to TB chemotherapy. The IDO inhibitor D-1 methyl tryptophan (D1MT) is, therefore, a bona fide TB HDT candidate. Since HDTs against TB are likely to be deployed in an HIV coinfection setting, we studied the effect of IDO inhibition in M. tuberculosis/SIV coinfection, adjunctive to cART. D1MT is safe in this setting, does not interfere with viral suppression, and improves the quality of CD4+ and CD8+ T cell responses, including reconstitution, activation and M. tuberculosis-specific cytokine production, and access of CD8+ T cells to the lung granulomas; it reduces granuloma size and necrosis, type I IFN expression, and the recruitment of inflammatory IDO+ interstitial macrophages (IMs). Thus, trials evaluating the potential of IDO inhibition as HDT in the setting of cART in M. tuberculosis/HIV coinfected individuals are warranted. |
| فهرسة مساهمة: | Keywords: Immunology; Infectious disease; Tuberculosis |
| المشرفين على المادة: | 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase) 8DUH1N11BX (Tryptophan) 0 (Anti-Retroviral Agents) 7303-49-3 (tryptophan methyl ester) |
| تواريخ الأحداث: | Date Created: 20240808 Date Completed: 20240808 Latest Revision: 20240808 |
| رمز التحديث: | 20240808 |
| DOI: | 10.1172/jci.insight.179317 |
| PMID: | 39114981 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2379-3708 |
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| DOI: | 10.1172/jci.insight.179317 |