MCP-1 production regulated by ATG5 in inflammatory monocytes selectively modulates anti-malarial CD4+ Th1 response
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ABSTRACT:
PROVIDER: PRJNA949962 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24003400_1.fastq.gz | Fastqsanger.gz | |||
| SRR24003400_2.fastq.gz | Fastqsanger.gz | |||
| SRR24003401_1.fastq.gz | Fastqsanger.gz | |||
| SRR24003401_2.fastq.gz | Fastqsanger.gz | |||
| SRR24003402_1.fastq.gz | Fastqsanger.gz |
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Project description:Induction of parasite-specific CD4+ Th1 cell responses is a promising strategy for designing effective blood-stage malaria vaccines; 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 enhancing parasite-specific CD4+ Th1 cell responses. This effect was independent of ATG5-mediated canonical and non-canonical autophagy. Mechanistically, ATG5 deficiency promoted myeloid cell (Ly6G-CD11b+F4/80-) survival and subsequently increased MCP-1 production in parasite-infected mice. Ly6G-CD11b+F4/80- cell-derived MCP-1 interacted with CCR2 on CD4+ Th1 cells for their optimized responses through the JAK2/STAT4 pathway. Notably, recombinant MCP-1 significantly improved parasite-specific CD4+ Th1 responses of the whole-killed blood-stage vaccine. Conclusively, our study highlights the previously unrecognized role of ATG5 in modulating myeloid cell survival via MCP-1 production, which selectively promotes CD4+ Th1 cell responses. Our findings provide new insights into the development of effective antimalarial vaccines.
2023-12-16 | GSE239405 | GEO
Project description:A promising strategy to design effective malaria blood-stage vaccines is to induce parasite-specific CD4+ Th1 cell responses, but the regulatory mechanism of which is still largely unknown. Here, we showed that the ATG5-deficiency in myeloid cells significantly inhibit the growth of rodent blood-stage malaria parasites through specifically enhancing parasite-specific CD4+ Th1 cell responses. This effect was independent of ATG5-mediated canonical autophagy and non-canonical autophagy. Mechanistically, the deficiency of ATG5 promoted the survival of inflammatory monocytes (CD11b+F4/80- cells), and sequentially increased the generation of chemokine MCP-1 in parasite-infected mice. The interaction of CD11b+F4/80- cells-derived MCP-1 with CCR2 on CD4+ Th1 cells for its optimized differentiation dependent on Jak2/stat4 pathway. Therefore, we highlight the previously unrecognized role of ATG5 in the modulation of the survival of inflammatory monocytes to produce MCP-1, and the selective promoting effect of MCP-1 on CD4+ Th1 cell differentiation, which shed new lights on effective malaria vaccine designation.
2024-03-01 | GSE228461 | GEO
Project description:ATG5-regulated MCP-1 production in myeloid cells selectively modulates anti-malarial CD4+ Th1 responses
| PRJNA999227 | ENA
Project description: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.
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Project description:Purpose: study of function of ATG5 protein on zebrafish larvae development Methods: Using morpholino oligos for atg5 gene knock down and overexpression, injected into one- to four-cell-stage embryos,extracted total RNA, then sending to RNA sequencing. Results: we compared to Wildtype, 5MO and atg5 mRNA groups, we analyza autophagy related gene mRNA expression, there are obvious different. Conclusion: our study showed the function of autophagy related gene 5 on zebrafish larvae, it has an important significant for understanding the affection of autophagy on embryo development
2019-04-30 | GSE120170 | GEO
Project description:Inflammation is critical for controlling infections but can cause disease when unchecked. For tuberculosis, the leading cause of death by infection, neutrophil-dominated inflammation is associated with disease progression, emphasizing the need to understand how neutrophil functions are regulated during Mycobacterium tuberculosis infection. Atg5 was the first gene shown to specifically function within neutrophils to promote control of M. tuberculosis. ATG5 is best studied for its role in autophagy, however, the protective activity of ATG5 in neutrophils was unexpectedly independent of other autophagy proteins and remained elusive. We report that ATG5 is required in neutrophils to suppress type I interferon-induced neutrophil extracellular trap (NET) release and swarming during M. tuberculosis infection. Elevated NET release contributes to the early susceptibility of Atg5fl/fl-LysM-Cre mice during infection. These findings identify ATG5 as a master regulator of how type I interferon influences neutrophil responses during infection, revealing a new potential target for host-directed therapies.
2025-03-07 | GSE280193 | GEO
Project description:Microarray analysis revealed MCP-1 treatment altered protein folding processes in RCC CRL1932 cells. In response to MCP-1 treatment, CRL1932 cells and xenograft tumors expressed MCP-1-induced protein (MCPIP) which was reported to cause endoplasmic reticulum (ER) stress-induced apoptosis in human cardiomyocytes. In line with MCPIP induction, the expression of ER stress mediators, such as GRP78, PERK, IRE1α, and PDI, as well as molecules involved in ER stress-induced apoptosis, CHOP, calnexin, and Ero1α, presented in MCP-1 treated RCC cell line and xenograft tumors whereas absent or downregulated in untreated controls. TUNEL assay confirmed apoptosis of MCP-1 treated CRL1932 cells. MCPIP ectopically expressed in HEK293 cell resulted in apoptosis. Meta-analysis showed low level of MCP-1 associated with lower one year-survival rate after nephrectomy in RCC. In this dataset, we include the expression array data from human kidney cancer CRL-1932 cell line with or without the treatment of MCP-1. These data were used to obtain genes upregulated in MCP-1-treated CRL-1932 cells.
2019-12-31 | GSE127996 | GEO
Project description:In order to understand the contribution of autophagy and alternative NF-kappaB signalling to transcriptional output in A549 lung cancer cells, RNAi was used to knockdown the expression of core autophagy genes (ATG5, ULK1) or the key subunit of alternative NF-kappaB RELB. Seven samples were prepared for each biological replicate; two sequence independent non-targeting control siRNAs were transfected as a negative control. Three sequence independent siRNAs targeting the core autophagy machinery were transfected (ATG5 si, ATG5 si(2), ULK1 si). N.B. ATG5 si(2) only partially ablates Atg5 protein expression whereas ATG si has greater efficacy. Two sequence independent siRNAs targeting RELB were transfected (RELB si, RELB si(2) ). Three independent biological replicates of all conditions were obtained, by performance of the experiment on different days.
2015-09-18 | E-GEOD-73158 | biostudies-arrayexpress
Project description:Autophagy plays an important role in physiology and tumorigenesis. We and others have demonstrated that Ha-ras overexpression induces autophagy in NIH3T3 cells. Autophagic machinery is regulated by a family of autophagy associated genes (Atg). The inducible Ha-ras oncogene was introduced into mouse embryo fibroblast Atg5 wild type [MEF-Atg5(+/+)] and Atg5 knock-out [MEF-Atg5(-/-)] cells and the stable cell lines MR and M5R were established, respectively. Our results showed that M5R cell induced larger tumor formation compared with MR cells while these two cell lines were subcutaneously injected into SCID mice under Ha-ras overexpression conditions. It indicates that Atg5 is involved in the suppression of Ras-related tumor formation. MicroRNA (miRNA), approximately 22 nucleotide of non-coding RNA, regulates transcription and translation of the target genes and is involved in cell differentiation and tumorigenesis. A miRNA microarray (932 probes) screening was conducted to identify the autophagy-tumorigenesis-related miRNAs. Among the significant genes, miR-224 was highly expressed in autophagy deficient cell and it induced tumors. Overexpression miR-224 enhanced the activity of migration and invasion in vitro and tumor formation in vivo. In conclusion, this is the first report to demonstrate that autophagy suppresses tumor formation through down-regulation of microRNA in this case miR-224. MR and M5R cell lines were treated with IPTG for 48 hr. In addition, these cell lines were subcutaneously injected into mice to induce tumor formation. The RNA samples were extracted from above cell lines and tumors. In this research, BEL/ITRI 15K V1.0 miRNA microarray chips were used to evaluate the miRNA expression profile.
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