دورية أكاديمية
A germ-free humanized mouse model shows the contribution of resident microbiota to human-specific pathogen infection.
العنوان: | A germ-free humanized mouse model shows the contribution of resident microbiota to human-specific pathogen infection. |
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المؤلفون: | Wahl A; International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. awahl@med.unc.edu.; Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. awahl@med.unc.edu.; Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. awahl@med.unc.edu., Yao W; International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Liao B; International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China., Chateau M; International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Richardson C; International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Ling L; International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Franks A; International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Senthil K; International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Doyon G; International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Li F; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Frost J; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Division of Comparative Medicine, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Whitehurst CB; Department of Pathology, Microbiology, and Immunology, New York Medical College, Valhalla, NY, USA., Pagano JS; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Fletcher CA; Division of Comparative Medicine, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Azcarate-Peril MA; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; UNC Microbiome Core, University of North Carolina, Chapel Hill, NC, USA., Hudgens MG; Department of Biostatistics, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Rogala AR; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Division of Comparative Medicine, Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Tucker JD; Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK., McGowan I; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, USA.; Orion Biotechnology, Ottawa, Ontario, Canada., Sartor RB; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Garcia JV; International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. victor_garcia@med.unc.edu.; Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. victor_garcia@med.unc.edu.; Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. victor_garcia@med.unc.edu.; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. victor_garcia@med.unc.edu. |
المصدر: | Nature biotechnology [Nat Biotechnol] 2024 Jun; Vol. 42 (6), pp. 905-915. Date of Electronic Publication: 2023 Aug 10. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Nature America Publishing Country of Publication: United States NLM ID: 9604648 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1696 (Electronic) Linking ISSN: 10870156 NLM ISO Abbreviation: Nat Biotechnol Subsets: MEDLINE |
أسماء مطبوعة: | Publication: New York Ny : Nature America Publishing Original Publication: New York, NY : Nature Pub. Co., [1996- |
مواضيع طبية MeSH: | Disease Models, Animal* , Microbiota* , Germ-Free Life* , HIV Infections*/immunology , HIV Infections*/microbiology, Animals ; Humans ; Mice ; Epstein-Barr Virus Infections/immunology ; Herpesvirus 4, Human/immunology ; CD4-Positive T-Lymphocytes/immunology ; HIV ; Gastrointestinal Microbiome |
مستخلص: | Germ-free (GF) mice, which are depleted of their resident microbiota, are the gold standard for exploring the role of the microbiome in health and disease; however, they are of limited value in the study of human-specific pathogens because they do not support their replication. Here, we develop GF mice systemically reconstituted with human immune cells and use them to evaluate the role of the resident microbiome in the acquisition, replication and pathogenesis of two human-specific pathogens, Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV). Comparison with conventional (CV) humanized mice showed that resident microbiota enhance the establishment of EBV infection and EBV-induced tumorigenesis and increase mucosal HIV acquisition and replication. HIV RNA levels were higher in plasma and tissues of CV humanized mice compared with GF humanized mice. The frequency of CCR5 + CD4 + T cells throughout the intestine was also higher in CV humanized mice, indicating that resident microbiota govern levels of HIV target cells. Thus, resident microbiota promote the acquisition and pathogenesis of two clinically relevant human-specific pathogens. (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.) |
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معلومات مُعتمدة: | U19 AI082637 United States AI NIAID NIH HHS; UM1 AI126619 United States AI NIAID NIH HHS; P30 DK034987 United States DK NIDDK NIH HHS; P30 CA016086 United States CA NCI NIH HHS; P30DK034987 U.S. Department of Health & Human Services | National Institutes of Health (NIH); DK131585 U.S. Department of Health & Human Services | National Institutes of Health (NIH); D43 TW009532 United States TW FIC NIH HHS; AI123010 U.S. Department of Health & Human Services | National Institutes of Health (NIH); P30 DK056350 United States DK NIDDK NIH HHS; 1UM1AI126619 U.S. Department of Health & Human Services | National Institutes of Health (NIH); P30 AI050410 United States AI NIAID NIH HHS; R34 MH119963 United States MH NIMH NIH HHS; U19AI082637 U.S. Department of Health & Human Services | National Institutes of Health (NIH); P40 OD010995 United States OD NIH HHS; P40OD010995 U.S. Department of Health & Human Services | National Institutes of Health (NIH); D43TW009532 U.S. Department of Health & Human Services | NIH | Fogarty International Center (FIC); R01 AI123010 United States AI NIAID NIH HHS; UM1 AI164567 United States AI NIAID NIH HHS; R01 DK131585 United States DK NIDDK NIH HHS |
تواريخ الأحداث: | Date Created: 20230810 Date Completed: 20240616 Latest Revision: 20240718 |
رمز التحديث: | 20240718 |
مُعرف محوري في PubMed: | PMC11073568 |
DOI: | 10.1038/s41587-023-01906-5 |
PMID: | 37563299 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1546-1696 |
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DOI: | 10.1038/s41587-023-01906-5 |