論文 - 詳細
| RRC ID | 89751 |
|---|---|
| 著者 | Gao Y, Chen S, Jiao S, Fan Y, Li X, Tan N, Fang J, Xu L, Huang Y, Zhao J, Guo S, Liu T, Xu W. |
| タイトル | ATG5-regulated CCL2/MCP-1 production in myeloid cells selectively modulates anti-malarial CD4+ Th1 responses. |
| ジャーナル | Autophagy |
| Abstract |
Parasite-specific CD4+ Th1 cell responses are the predominant immune effector for controlling malaria infection; however, the underlying regulatory mechanisms remain largely unknown. This study demonstrated that ATG5 deficiency in myeloid cells can significantly inhibit the growth of rodent blood-stage malarial parasites by selectively enhancing parasite-specific CD4+ Th1 cell responses. This effect was independent of ATG5-mediated canonical and non-canonical autophagy. Mechanistically, ATG5 deficiency suppressed FAS-mediated apoptosis of LY6G- ITGAM/CD11b+ ADGRE1/F4/80- cells and subsequently increased CCL2/MCP-1 production in parasite-infected mice. LY6G- ITGAM+ ADGRE1- cell-derived CCL2 selectively interacted with CCR2 on CD4+ Th1 cells for their optimized responses through the JAK2-STAT4 pathway. The administration of recombinant CCL2 significantly promoted parasite-specific CD4+ Th1 responses and suppressed malaria infection. Conclusively, our study highlights the previously unrecognized role of ATG5 in modulating myeloid cells apoptosis and sequentially affecting CCL2 production, which selectively promotes CD4+ Th1 cell responses. Our findings provide new insights into the development of immune interventions and effective anti-malarial vaccines.Abbreviations: ATG5: autophagy related 5; CBA: cytometric bead array; CCL2/MCP-1: C-C motif chemokine ligand 2; IgG: immunoglobulin G; IL6: interleukin 6; IL10: interleukin 10; IL12: interleukin 12; MFI: mean fluorescence intensity; JAK2: Janus kinase 2; LAP: LC3-associated phagocytosis; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; pRBCs: parasitized red blood cells; RUBCN: RUN domain and cysteine-rich domain containing, Beclin 1-interacting protein; STAT4: signal transducer and activator of transcription 4; Th1: T helper 1 cell; Tfh: follicular helper cell; ULK1: unc-51 like kinase 1. |
| 巻・号 | 20(6) |
| ページ | 1398-1417 |
| 公開日 | 2024-6-1 |
| DOI | 10.1080/15548627.2024.2319512 |
| PMID | 38368631 |
| PMC | PMC11210915 |
| MeSH | Animals Apoptosis / drug effects Autophagy / drug effects Autophagy-Related Protein 5* / metabolism CD4-Positive T-Lymphocytes / immunology CD4-Positive T-Lymphocytes / metabolism Chemokine CCL2* / metabolism Malaria* / immunology Malaria* / parasitology Mice Mice, Inbred C57BL Myeloid Cells* / metabolism Plasmodium berghei / immunology Signal Transduction / drug effects Th1 Cells* / immunology |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC02975 |