| 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
|
| リソース情報 |
| 実験動物マウス |
RBRC02975 |
