Rag2 Deficiency Enhances Susceptibility to Systemic Mouse Adenovirus Type 1 Infection
| Autor: | Yang-Kyu Choi, Han-Woong Kim, Jun-Young Kim, Eui-Suk Jeong, Han-Kyul Lee, Sun-Min Seo |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Chemokine
medicine.medical_treatment T cell animal diseases Adenoviridae Infections Specialties of internal medicine Spleen Inflammation Recombination-activating gene Adenoviridae Mice Downregulation and upregulation RAG2 Virology medicine Animals Mice Knockout biology business.industry DNA-Binding Proteins Mice Inbred C57BL Infectious Diseases Cytokine medicine.anatomical_structure RC581-951 Immunology biology.protein Cytokines Severe Combined Immunodeficiency medicine.symptom business |
| Zdroj: | Intervirology (2021) |
| ISSN: | 1423-0100 |
| Popis: | Introduction: Recombination-activating gene (Rag) 1 and Rag2, which are essential in V(D)J recombination, play a crucial role in B- and T-cell maturation. Method: We investigated the effects of Rag2 deficiency in clustered regularly interspaced short palindromic repeats/Cas9-mediated FVB-Rag2 knockout (KO) and wild-type (WT) mice infected with mouse adenovirus type 1 (MAV-1) via the intranasal route. Results: MAV-1 infection caused more severe histopathological changes in FVB-Rag2 KO mice than in WT mice. FVB-Rag2 KO mice exhibited moderate to severe inflammation on day 4 and severe inflammation on day 8 post infection. In contrast, WT mice showed mild inflammation on day 4 and mild to severe inflammation on day 8 post infection, including interstitial pneumonia and inflammatory cell infiltration in the lungs and liver. Viral loads in the spleen and kidneys were significantly higher in FVB-Rag2 KO mice than in WT mice on day 8 post infection. Levels of cytokines and chemokines, including macrophage inflammatory protein-1α, induced protein 10, interferon (IFN)-α, IFN-γ, and tumor necrosis factor alpha, were upregulated in the spleens of FVB-Rag2 KO mice compared with those of WT mice. The upregulation of several cytokines occurred concurrently with the histopathological changes. MAV-1 infection induced more severe systemic infection in FVB-Rag2 KO mice than in WT mice. Conclusion: In mice, Rag2 deficiency induces inflammatory cell recruitment via the upregulation of cytokine and chemokine levels. The MAV-1 infection model can be utilized to assess the efficacy and safety of therapeutic agents for human adenoviral diseases. |
| Databáze: | OpenAIRE |
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