Crosstalk Between Autophagy and Hypoxia-Inducible Factor-1α in Antifungal Immunity

Quäschling, Tim; Friedrich, Dirk; Deepe, George S.; Rupp, Jan

doi:10.3390/cells9102150

Cited by 12 publications

(7 citation statements)

References 63 publications

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“…Hypoxia in the tumor microenvironment regulates the function of immune cell effectors and plays a positive role in tumor development ( 18 ). Although there is a clear link between hypoxia and immunity ( 42 , 43 ), fewer studies pay attention to the comprehensive molecular mechanism.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia–Immune-Related Gene SLC19A1 Serves as a Potential Biomarker for Prognosis in Multiple Myeloma

Yuan

Liu

et al. 2022

Front. Immunol.

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BackgroundMultiple myeloma (MM) remains an incurable malignant tumor of plasma cells. Increasing evidence has reported that hypoxia and immune status contribute to the progression of MM. In this research, the prognostic value of the hypoxia–immune-related gene SLC19A1 in MM was evaluated by bioinformatics analysis.MethodRNA-sequencing (RNA-seq) data along with clinical information on MM were downloaded from the Gene Expression Omnibus (GEO) database. Consistent clustering analysis and ESTIMATE algorithms were performed to establish the MM sample subgroups related to hypoxia and immune status, respectively, based on the GSE24080 dataset. The differentially expressed analysis was performed to identify the hypoxia–immune-related genes. Subsequently, a hypoxia–immune-gene risk signature for MM patients was constructed by univariate and multivariate Cox regression analyses, which was also verified in the GSE4581 dataset. Furthermore, the mRNA expression of SLC19A1 was determined using qRT-PCR in 19 MM patients, and the correlations between the genetic expression of SLC19A1 and clinical features were further analyzed.ResultA total of 47 genes were identified as hypoxia–immune-related genes for MM. Among these genes, SLC19A1 was screened to construct a risk score model that had better predictive power for MM. The constructed prognostic signature based on SLC19A1 was verified in the GSE4581 dataset. All independent prognostic factors (age, β2-microglobulin, LDH, albumin, MRI, and gene risk score) were used to develop a nomogram that showed a better performance for predicting the survival probability of MM patients for 1–5 years. Furthermore, SLC19A1 was highly expressed in newly diagnosed and relapsed MM patients, and high expression of SLC19A1 is correlated with higher bone marrow aspiration plasma cells and β2-microglobulin levels in MM patients.ConclusionIn conclusion, our results suggest that SLC19A1 is aberrantly expressed in MM and highly expressed SLC19A1 might be a biomarker correlated with inferior prognosis. More importantly, we identified SLC19A1 as a hypoxia–immune-related gene in MM. Future functional and mechanistic studies will further clarify the roles of SLC19A1 in MM.

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Section: Discussionmentioning

confidence: 99%

Hypoxia–Immune-Related Gene SLC19A1 Serves as a Potential Biomarker for Prognosis in Multiple Myeloma

Yuan

Liu

et al. 2022

Front. Immunol.

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“…In the interaction of macrophages with H. capsulatum , Hif1α was shown to limit fungal intracellular survival by reducing the recruitment of LC3-II to the fungal phagosome. In this case, H. capsulatum exploits host autophagy to survive [ 87 , 88 ]. Contrastingly, results from a parallel project from our group suggest that, in the interaction of different macrophages with P. brasiliensis , LAP is detrimental for the fungus, reinforcing this process’s potential role in macrophage ability to deal with this pathogen.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with Paracoccidioides brasiliensis: More Is Not Necessarily Better

de-Souza-Silva

Hurtado

Tavares

et al. 2020

JoF

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Most people infected with the fungus Paracoccidioides spp. do not get sick, but approximately 5% develop paracoccidioidomycosis. Understanding how host immunity determinants influence disease development could lead to novel preventative or therapeutic strategies; hence, we used two mouse strains that are resistant (A/J) or susceptible (B10.A) to P. brasiliensis to study how dendritic cells (DCs) respond to the infection. RNA sequencing analysis showed that the susceptible strain DCs remodeled their transcriptomes much more intensely than those from the resistant strain, agreeing with a previous model of more intense innate immunity response in the susceptible strain. Contrastingly, these cells also repress genes/processes involved in antigen processing and presentation, such as lysosomal activity and autophagy. After the interaction with P. brasiliensis, both DCs and macrophages from the susceptible mouse reduced the autophagy marker LC3-II recruitment to the fungal phagosome compared to the resistant strain cells, confirming this pathway’s repression. These results suggest that impairment in antigen processing and presentation processes might be partially responsible for the inefficient activation of the adaptive immune response in this model.

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“…In lipopolysaccharide (LPS)-exposed macrophages, the tricarboxylic acid (TCA) cycle intermediate succinate stimulates IL-1β production via HIF-1α activation ( 89 ). Recent studies highlight that HIF-1α is required for canonical and noncanonical autophagy to impact antifungal immunity ( 90 , 91 ). However, it remains elucidated whether Akt/mTOR/HIF-1α signaling coordinates aerobic glycolysis and autophagy pathway to regulate host defense against Mtb infection.…”

Section: The Mtor Pathway Links Autophagy and Immunometabolismmentioning

confidence: 99%

An Interplay Between Autophagy and Immunometabolism for Host Defense Against Mycobacterial Infection

Paik

2020

Front. Immunol.

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Autophagy, an intracellular catabolic pathway featuring lysosomal degradation, is a central component of the host immune defense against various infections including Mycobacterium tuberculosis (Mtb), the pathogen that causes tuberculosis. Mtb can evade the autophagic defense and drive immunometabolic remodeling of host phagocytes. Co-regulation of the autophagic and metabolic pathways may play a pivotal role in shaping the innate immune defense and inflammation during Mtb infection. Two principal metabolic sensors, AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) kinase, function together to control the autophagy and immunometabolism that coordinate the anti-mycobacterial immune defense. Here, we discuss our current understanding of the interplay between autophagy and immunometabolism in terms of combating intracellular Mtb, and how AMPK-mTOR signaling regulates antibacterial autophagy in terms of Mtb infection. We describe several autophagy-targeting agents that promote host antimicrobial defenses by regulating the AMPK-mTOR axis. A better understanding of the crosstalk between immunometabolism and autophagy, both of which are involved in host defense, is crucial for the development of innovative targeted therapies for tuberculosis.

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Crosstalk Between Autophagy and Hypoxia-Inducible Factor-1α in Antifungal Immunity

Cited by 12 publications

References 63 publications

Hypoxia–Immune-Related Gene SLC19A1 Serves as a Potential Biomarker for Prognosis in Multiple Myeloma

Hypoxia–Immune-Related Gene SLC19A1 Serves as a Potential Biomarker for Prognosis in Multiple Myeloma

Transcriptional Remodeling Patterns in Murine Dendritic Cells Infected with Paracoccidioides brasiliensis: More Is Not Necessarily Better

An Interplay Between Autophagy and Immunometabolism for Host Defense Against Mycobacterial Infection

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