A network of immune and microbial modifications underlies viral persistence in the gastrointestinal tract
| Autor: | Bethany L. MacLeod, Laura M. Snell, Russell J. Dickson, Kebria Hezaveh, Cynthia J. Guidos, Mengdi Guo, Heidi Elsaesser, W. Xu, Tracy L. McGaha, David G. Brooks, Akash Kothari |
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| Rok vydání: | 2019 |
| Předmět: |
Immunology
Cell Innate Immunity and Inflammation chemical and pharmacologic phenomena Spleen Biology CD8-Positive T-Lymphocytes Lymphocytic Choriomeningitis Lymphocyte Activation T-Lymphocytes Regulatory Lymphocyte Depletion Technical Advances and Resources Infectious Disease and Host Defense 03 medical and health sciences 0302 clinical medicine Immune system medicine Immunology and Allergy Animals Lymphocytic choriomeningitis virus Mass cytometry Receptor 030304 developmental biology 0303 health sciences Gastrointestinal tract Bystander Effect Mucosal Immunology Colitis 3. Good health Gastrointestinal Tract Mice Inbred C57BL Chronic infection medicine.anatomical_structure Phenotype Gene Expression Regulation 030220 oncology & carcinogenesis Chronic Disease Dysbiosis Transcriptome CD8 |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 |
| Popis: | Macleod et al. uncover how chronic viral infection modulates gastrointestinal immune and microbial composition to foster persistence and long-term disease susceptibilities. The authors also identify the central role of regulatory T cells to maintain viral sanctuary in the intestinal tract. Many pathogens subvert intestinal immunity to persist within the gastrointestinal tract (GIT); yet, the underlying mechanisms that enable sanctuary specifically in this reservoir are unclear. Using mass cytometry and network analysis, we demonstrate that chronic LCMV infection of the GIT leads to dysregulated microbial composition, a cascade of metabolic alterations, increased susceptibility to GI disease, and a system-wide recalibration of immune composition that defines viral persistence. Chronic infection led to outgrowth of activated Tbet–expressing T reg cell populations unique to the GIT and the rapid erosion of pathogen-specific CD8 tissue-resident memory T cells. Mechanistically, T reg cells and coinhibitory receptors maintained long-term viral sanctuary within the GIT, and their targeting reactivated T cells and eliminated this viral reservoir. Thus, our data provide a high-dimensional definition of the mechanisms of immune regulation that chronic viruses implement to exploit the unique microenvironment of the GIT and identify T reg cells as key modulators of viral persistence in the intestinal tract. Graphical Abstract |
| Databáze: | OpenAIRE |
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