Gut germinal center regeneration and enhanced antiviral immunity by mesenchymal stem/stromal cells in SIV infection
| Autor: | Weber, Mariana G, Walters-Laird, Chara J, Kol, Amir, Santos Rocha, Clarissa, Hirao, Lauren A, Mende, Abigail, Balan, Bipin, Arredondo, Juan, Elizaldi, Sonny R, Iyer, Smita S, Tarantal, Alice F, Dandekar, Satya |
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| Rok vydání: | 2021 |
| Předmět: |
5.2 Cellular and gene therapies
Prevention Inflammatory and immune system Simian immunodeficiency virus Immunity Simian Acquired Immunodeficiency Syndrome Humoral Mesenchymal Stem Cells Cellular immune response Germinal Center Mesenchymal Stem Cell Transplantation Regenerative Medicine Macaca mulatta AIDS/HIV Vaccine Related Infectious Diseases Good Health and Well Being Cytokines HIV/AIDS Animals Immunization Development of treatments and therapeutic interventions Intestinal Mucosa Infection Vaccine Related (AIDS) |
| Zdroj: | JCI insight, vol 6, iss 12 |
| Popis: | Although antiretroviral therapy suppresses HIV replication, it does not eliminate viral reservoirs or restore damaged lymphoid tissue, posing obstacles to HIV eradication. Using the SIV model of AIDS, we investigated the effect of mesenchymal stem/stromal cell (MSC) infusions on gut mucosal recovery, antiviral immunity, and viral suppression and determined associated molecular/metabolic signatures. MSC administration to SIV-infected macaques resulted in viral reduction and heightened virus-specific responses. Marked clearance of SIV-positive cells from gut mucosal effector sites was correlated with robust regeneration of germinal centers, restoration of follicular B cells and T follicular helper (Tfh) cells, and enhanced antigen presentation by viral trapping within the follicular DC network. Gut transcriptomic analyses showed increased antiviral response mediated by pathways of type I/II IFN signaling, viral restriction factors, innate immunity, and B cell proliferation and provided the molecular signature underlying enhanced host immunity. Metabolic analysis revealed strong correlations between B and Tfh cell activation, anti-SIV antibodies, and IL-7 expression with enriched retinol metabolism, which facilitates gut homing of antigen-activated lymphocytes. We identified potentially new MSC functions in modulating antiviral immunity for enhanced viral clearance predominantly through type I/II IFN signaling and B cell signature, providing a road map for multipronged HIV eradication strategies. |
| Databáze: | OpenAIRE |
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